Autoimmune encephalitis in a resource-limited public health setting: a case series analysis / Encefalite autoimune em um hospital universitário público: análise de uma série de casos

Abstract Background Autoimmune encephalitis (AE) consists of a group of acquired diseases that affect the central nervous system. A myriad of phenotypes may be present at the onset. Due to the heterogeneity of clinical presentations, it is difficult to achieve uniformity for the diagnostic and therapeutic processes and follow-up strategies. Objective To describe a series of patients diagnosed with AE in a resource-limited public hospital in southern Brazil and to analyze therapeutics and outcomes. Methods We retrospectively reviewed the electronic medical records of patients diagnosed with AE at the Hospital de Clínicas de Porto Alegre from 2014 to 2022. Data collected included clinical presentation, neuroimaging, cerebrospinal fluid testings, electroencephalogram, autoantibodies, treatments, outcomes, follow-up time, degree of neurological impairment, and mortality. Results Data from 17 patients were retrieved. Eleven cases were classified as definite AE and 6 as possible AE. Autoantibodies were identified in 9 patients. Timing for diagnosis was impacted by the high costs associated with autoantibody testing. Most patients became functionally dependent (82.4%) and most survivors remained with autoimmune-associated epilepsy (75%). Five patients died during hospitalization, and one after a 26-month of follow-up. Conclusion In this resource-limited hospital, patients with AE had a worse clinical outcome than that previously described in the literature. Development of epilepsy during follow-up and mortality were greater, whilst functional outcome was inferior. Autoantibody testing was initially denied in most patients, which impacted the definitive diagnosis and the use of second-line therapies.

Resumo Antecedentes A encefalite autoimune (EA) consiste em um grupo de doenças adquiridas que afetam o sistema nervoso central. Objetivo Descrever uma série de pacientes diagnosticados com EA em um contexto de atenção terciária à saúde com recursos limitados e analisar a terapêutica e os resultados. Métodos Revisamos retrospectivamente os prontuários eletrônicos de pacientes diagnosticados com EA no Hospital de Clínicas de Porto Alegre de 2014 a 2022. Os dados coletados incluíram apresentação clínica, neuroimagem, exames de líquido cefalorraquidiano, eletroencefalograma, autoanticorpos, tratamentos, resultados, tempo de acompanhamento, grau de comprometimento neurológico e mortalidade. Resultados Dados de 17 pacientes foram coletados. Onze casos foram classificados como EA definitivo e seis como EA possível. Autoanticorpos foram identificados em nove pacientes. O tempo para o diagnóstico foi afetado pelos altos custos associados ao teste de autoanticorpos. A maioria dos pacientes tornou-se funcionalmente dependente (82,4%), e a maioria dos sobreviventes permaneceu com epilepsia autoimune associada (75%). Cinco pacientes faleceram durante a internação, e um após 26 meses de seguimento. Conclusão No hospital em questão, os pacientes com EA tiveram um desfecho clínico pior do que o previamente descrito na literatura. O desenvolvimento de epilepsia durante o acompanhamento e a mortalidade foram maiores, enquanto o desfecho funcional foi inferior. Os testes de autoanticorpos foram inicialmente negados para a maioria dos pacientes, o que impactou o diagnóstico definitivo e o uso de terapias de segunda linha.

Síndrome de la persona rígida asociado a timoma / Stiff person syndrome associated with thymoma

Resumen El síndrome de persona rígida es un cuadro neuro lógico infrecuente caracterizado por rigidez muscular de tronco y extremidades y espasmos musculares ga tillados por estímulos sensoriales o emocionales, que progresa hacia la postración. Cuenta con un mecanismo fisiopatogénico con base inmunológica, en el cual los autoanticuerpos, como el antiGAD65, cumplen un rol central. Asimismo, la detección de dichos anticuerpos corrobora el diagnóstico ante un paciente con cuadro clínico sugestivo. Un 4 a 6% de los casos tienen neoplasias subyacentes. El tratamiento se basa en el manejo sintomático, inmunomodulador y de la enfermedad de base en los casos paraneoplásicos. Reportamos un caso de síndrome de persona rígida clásico asociado a timoma y describimos las características principales de esta entidad.

Abstract Stiff-person syndrome is a rare neurological condi tion characterized by muscular rigidity of the trunk and extremities and muscle spasms triggered by sensory or emotional stimuli, which progresses towards prostra tion. It has a pathophysiogenic mechanism with an immunological basis, in which autoantibodies, such as antiGAD65, play a central role. Likewise, the detec tion of these antibodies corroborates the diagnosis in a patient with a suggestive clinical picture. Four to 6% of cases have underlying neoplasms. Treatment is based on symptomatic, immunomodulatory, and underlying disease management in paraneoplastic cases. We re port a case of classic stiff person syndrome associated with thymoma and review the main characteristics of this entity.

Presencia de autoanticuerpos anti islotes pancreáticos en diabetes tipo 1 durante la edad pediátrica / Presence of anti-pancreatic islet autoantibodies in type 1 diabetes in children

En la Diabetes tipo 1 (DM1) la pérdida de células ß pancreáticas es consecuencia de un proceso de autoinmunidad que cursa con la presencia de autoanticuerpos anti-islotes pancreáticos (AAPs). Estos AAPs son marcadores útiles para la clasificación de la enfermedad. En un centro pediátrico de tercer nivel se analizó la frecuencia de presentación de GADA, IA-2A, ZnT8A e IAA en un grupo con reciente debut entre enero 2018 y agosto 2021 (n= 90). Además, se investigó la frecuencia de presentación y relación de los AAPs con la edad, sexo y tiempo de evolución en pacientes en seguimiento (n= 240). En el grupo de debut se obtuvo positividad de GADA, IA-2A, ZnT8A y IAA en 77,8; 60; 62 y 47,8% de los pacientes respectivamente, un 4% no presentó AAPs. El 95,6% de los pacientes presentaron al menos un AAPs positivo. La frecuencia de IAA en el grupo en debut fue mayor en menores de 5 años. En el grupo en seguimiento el 75,2% resultaron GADA positivo (85,7% en mujeres y 62,8% en varones) p<0,05. IA-2A y ZnT8A fueron positivos en 45 y 51.7% respectivamente. El 91% presentaron al menos un AAP positivo. En este grupo se evidenció una menor positividad en función del tiempo de evolución. Se pudo determinar la frecuencia de presentación de los AAPs en un grupo en debut y la relación con la edad, sexo y tiempo de evolución en pacientes en seguimiento. La determinación de APPs facilita la correcta clasificación y elección de la terapia adecuada (AU)

In type 1 diabetes (DM1) the loss of pancreatic ß-cells is a consequence of an autoimmune process that results in the presence of pancreatic anti-islet autoantibodies (PAAs). PAAs are useful markers for the classification of the disease. The frequency of presentation of GADA, IA-2A, ZnT8A, and IAA in a group with recent debut seen between January 2018 and August 2021 (n= 90) was analyzed in a tertiary pediatric center. In addition, we investigated the frequency of presentation and association of PAAs with age, sex, and time of evolution in patients in follow-up (n= 240). In the debut group, GADA, IA2A, ZnT8A, and IAA positivity was found in 77.8, 60, 62, and 47.8% of patients, respectively; no PAAs were observed in 4% of the patients. Overall, 95.6% presented at least one positive PAA. The frequency of IAA in the debut group was higher in children younger than 5 years. In the follow-up group, 75.2% were GADA positive (85.7% of females and 62.8% of males) p<0.05. IA-2A and ZnT8A were positive in 45 and 51.7% respectively. Ninety-one percent presented with at least one positive PAA. In this group, a lower positivity was evidenced as a function of the time of evolution. The frequency of presentation of PAAs in a debut group and the relationship with age, sex, and time of evolution in patients in follow-up was demonstrated. The assessment of PAAs facilitates the correct classification and choice of adequate therapy (AU)

Membranous nephropathy / Nefropatia membranosa

ABSTRACT Membranous nephropathy is a glomerulopathy, which main affected target is the podocyte, and has consequences on the glomerular basement membrane. It is more common in adults, especially over 50 years of age. The clinical presentation is nephrotic syndrome, but many cases can evolve with asymptomatic non-nephrotic proteinuria. The mechanism consists of the deposition of immune complexes in the subepithelial space of the glomerular capillary loop with subsequent activation of the complement system. Great advances in the identification of potential target antigens have occurred in the last twenty years, and the main one is the protein "M-type phospholipase-A2 receptor" (PLA2R) with the circulating anti-PLA2R antibody, which makes it possible to evaluate the activity and prognosis of this nephropathy. This route of injury corresponds to approximately 70% to 80% of cases of membranous nephropathy characterized as primary. In the last 10 years, several other potential target antigens have been identified. This review proposes to present clinical, etiopathogenic and therapeutic aspects of membranous nephropathy in a didactic manner, including cases that occur during kidney transplantation.

RESUMO A nefropatia membranosa é uma glomerulopatia, cujo principal alvo acometido é o podócito, e acarreta consequências na membrana basal glomerular. Tem maior frequência em adultos, principalmente acima dos 50 anos. A apresentação clínica é a síndrome nefrótica, mas muitos casos podem evoluir com proteinúria não nefrótica assintomática. O mecanismo consiste na deposição de complexos imunes no espaço subepitelial da alça capilar glomerular com subsequente ativação do sistema do complemento. Grandes avanços na identificação de potenciais antígenos alvo têm ocorrido nos últimos vinte anos, e o principal é a proteína "M-type phospholipase-A2 receptor" (PLA2R) com o anticorpo anti-PLA2R circulante, o que possibilita avaliar a atividade e o prognóstico dessa nefropatia. Essa via de lesão corresponde aproximadamente a 70% a 80% dos casos da nefropatia membranosa caracterizada como primária. Nos últimos 10 anos vários outros antígenos alvo potenciais têm sido identificados. Esta revisão se propõe a apresentar de modo didático aspectos clínicos, etiopatogênicos e terapêuticos da nefropatia membranosa, incluídos os casos com ocorrência no transplante renal.

Anti-ribosomal P (anti-P) antibodies in patients with autoimmune hepatitis

ABSTRACT Objective Published studies have shown associations between anti-ribosomal P (anti-P) antibody and systemic lupus erythematosus with hepatic manifestations. This has been reported also in autoimmune hepatitis. However, the consistency of the latter association remains controversial. This study aimed to evaluate the frequency of anti-P antibodies in autoimmune hepatitis using two different immunoassays. Methods One-hundred and seventy-seven patients with autoimmune hepatitis were screened, and 142 were analyzed for anti-P antibody positivity. The samples were first analyzed using two different immunoassays: enzyme-linked immunosorbent assay (ELISA) and chemiluminescence and then compared with a group of 60 patients with systemic lupus erythematous. The positive samples were subjected to western blot analysis. Results Anti-P was found in 5/142 autoimmune hepatitis cases (3.5%) by chemiluminescence and in none by ELISA. Among the five chemiluminescence-positive autoimmune hepatitis samples, on anti-P western blot analysis one was negative, two were weakly positive, and two were positive. In contrast, anti-P was detected in 10/60 patients with systemic lupus erythematosus (16.7%) and presented higher chemiluminescence units than the autoimmune hepatitis samples. Conclusion A low frequency of anti-P antibodies was observed in autoimmune hepatitis, suggesting that this test is not useful for the diagnosis or management of this disease.

Is there an association between endometriosis and thyroid autoimmunity?

SUMMARY OBJECTIVE: It has been suggested that non-uterine endometrial implants can express thyroid-stimulating hormone receptors, thus inducing the formation of thyroid-stimulating immunoglobulin. We aimed to compare the autoantibody positivity in patients with and without endometriosis and to determine whether there is a difference in the incidence of thyroid diseases. METHODS: This prospective observational study was conducted on 102 women who had been operated on for benign gynecological diseases. Cases enrolling in the study were divided into two groups: the study group with endometriosis (n=51) and the control group without endometriosis (n=51). The blood tests for thyroid-stimulating hormone, free thyroxine (fT4), thyroid-stimulating immunoglobulin, and anti-thyroid peroxidase antibody levels were checked. RESULTS: The mean thyroid-stimulating immunoglobulin level was found to be higher in the endometriosis group than in the control group. However, this difference was not statistically significant. No significant difference was detected between endometriosis and control groups in terms of anti-thyroid peroxidase antibody and thyroid-stimulating hormone levels. The mean fT4 value (0.97±0.13 ng/dL) of the endometriosis patients was found to be significantly lower than the control group (1.08±0.21 ng/dL) (p=0.002; p<0.05). The mean anti-thyroid peroxidase antibody value of cases with bilateral endometrioma (82.21±252.29 IU/mL) was significantly higher than cases with unilateral endometrioma (15.81±83.13 IU/mL) (p=0.028; p<0.05). There is a positive and significant relationship between the size of endometriosis and anti-thyroid peroxidase antibody values (p=0.011; p<0.05). CONCLUSION: This study points to an association between endometrioma diameter and anti-thyroid peroxidase antibody values which can be a stepping stone for new studies evaluating this hypothesis further.

Correlation between iodine nutrition and thyroid function of pregnant women in Xinjiang Uygur Autonomous Region / 中华地方病学杂志

Objective:Through the detection of iodine nutrition level and thyroid function of pregnant women in Xinjiang Uygur Autonomous Region (Xinjiang), to preliminary study the pregnant women's iodine nutrition level, thyroid function status and the relationship between the two and influencing factors.Methods:From March to June in 2020, stratified cluster random sampling method was adopted. Two counties (cities) in Southern and Northern Xinjiang were selected as survey sites, and about 100 pregnant women (a total of 412) were selected from each county (city) as survey subjects. Random urine samples and blood samples were collected to detect urinary iodine and serum thyroid function indicators [thyroid stimulating hormone (TSH), free triiodothyronine (FT 3), free thyroxine (FT 4), anti-thyroglobulin antibody (Tg-Ab) and anti-thyroid peroxidase antibody (TPO-Ab)]. Results:The median and interquartile range [ M ( Q1, Q3)] of pregnant women's urinary iodine was 228.4 (143.15, 327.95) μg/L. Serum FT 3, FT 4 and TSH levels [ M ( Q1, Q3)] were 4.22 (3.92, 4.61), 13.79 (12.63, 15.26) pmol/L and 1.82 (1.26, 2.52) mU/L, respectively. The overall positive rates of Tg-Ab and TPO-Ab were 5.61% (23/412) and 11.95% (49/412), respectively. The positive rates of Tg-Ab and TPO-Ab in Southern and Northern Xinjiang were 4.78% (10/209), 10.05% (21/209), 6.40% (13/203) and 13.79% (28/203), respectively. The positive rates of Tg-Ab and TPO-Ab in Northern Xinjiang were higher than those in Southern Xinjiang, but the difference was not statistically significant (χ 2 = 1.31, 2.17, P > 0.05). The positive rate of TPO-Ab in pregnant women was the influencing factor of abnormal thyroid function, and the odds ratio ( OR) [95% confidence interval ( CI)] was 3.22 (1.31 - 7.93). Conclusions:Pregnant women in Xinjiang are generally at an appropriate level of iodine, but the state of thyroid function still needs continuous attention. In addition, it is necessary to strengthen the thyroid function examination of pregnant women with positive thyroid autoantibodies to prevent and control the occurrence of abnormal thyroid function in pregnant women.

Application value of color Doppler ultrasonography combined with thyroid autoantibody detection in early diagnosis of thyroid cancer / 中国医师进修杂志

Objective:To investigate the clinical significance of color Doppler ultrasonography combined with detection of thyroid autoantibodies in the early diagnosis of thyroid cancer.Methods:A total of 108 patients with thyroid cancer who treated in Shaoxing Central Hospital Medical Community General Hospital from September 2019 to September 2021 were selected as the research group, and 108 patients with benign thyroid lesions during the same period were selected as the control group. The ultrasound examination results and the levels of serum thyroglobulin antibody (TgAb), thyroid peroxidase antibody (TPOAb) and thyroid receptor antibody (TRAb) were compared between the two groups. The relationship between the thyroid autoantibodies index and the early diagnosis of thyroid cancer were analyzed by Spearman correlation analysis; the value of early diagnosis by color Doppler ultrasonography combined with detection of thyroid autoantibodies were evaluated by the receiver operating characteristic (ROC) curve.Results:The main features of ultrasonic images in the research group were unclear edge, low echo, irregular shape, chaotic blood flow distribution, internal micro calcification, no envelope and blood flow resistance index ≥0.7. The sensitivity of ultrasonography for the diagnosis of thyroid cancer was 86.11% (93/108), the specificity was 87.18% (102/117) and the accuracy was 90.28% (195/216). The levels of serum TgAb, TPOAb and TRAb in the research group were higher than those in control group: (32.28 ± 2.85) kU/L vs. (21.96 ± 2.54) kU/L, (81.28 ± 7.32) kU/L vs. (51.53 ± 5.86) kU/L, (4.48 ± 1.25) U/L vs. (2.35 ± 0.63 ) U/L, there were statistical differences ( P<0.05). The levels of serum TgAb, TPOAb and TRAb in patients with lymph node metastasis were higher than those in the patients without lymph node metastasis: (36.28 ± 3.12) kU/L vs. (30.60 ± 2.54) kU/L, (93.51 ± 8.57) kU/L vs. (76.13 ± 6.62) kU/L, (5.73 ± 1.54) U/L vs. (3.95 ± 1.12) U/L, there were statistical differences ( P<0.05). The levels of serum TgAb, TPOAb and TRAb in patients with stage Ⅲ-Ⅳ were higher than those in the patients with stage Ⅰ-Ⅱ: (35.84 ± 3.28) kU/L vs. (29.74 ± 2.29) kU/L, (89.35 ± 8.16) kU/L vs. (75.52 ± 6.23) kU/L, (5.28 ± 1.49) U/L vs. (3.91 ± 1.25) U/L, there were statistical differences ( P<0.05). The results of Spearman correlation analysis showed that the levels of serum TgAb, TPOAb and TRAb were positively correlated with lymph node metastasis ( r = 0.758, 0.824, 0.695, P<0.05) and clinical stage of thyroid cancer ( r = 0.735, 0.796, 0.673, P<0.05). The results of ROC curve analysis showed that the area under the curve(AUC) of ultrasound examination combined with TgAb, TPOAb and TRAb for early diagnosis of thyroid cancer was 0.930, the sensitivity was 85.19%, and the specificity was 91.67%. The combined diagnostic value was better than single diagnosis. Conclusions:Ultrasound examination combined with serum TgAb, TPOAb and TRAb has high diagnostic value for early stage thyroid cancer, which is helpful to clinically clarify the condition, and provides a reliable basis for preoperative diagnosis and targeted individualized treatment plan.

Blood matching incompatibility caused by cold autoantibodies and IgG anti S antibody: a case report / 中国输血杂志

【Objective】 To analyze the serological characteristics of an anemia patient with cold autoantibodies and IgG anti S antibody. 【Methods】 Unexpected antibody screening was performed on screening cells, autologous cells and panel cells with patient serum in saline and anti human globulin card media at room temperature and 37 ℃, respectively. At the same time, the serum that destroying IgM antibodies and acid elution solution were respectively screened for unexpected antibodies in anti human globulin card media. The absorption-elution test was used to treat patients′ red blood cells and serum, and the unexpected antibody identification and cross matching were performed after excluding the interference of cold autoantibodies. 【Results】 Cold autoantibodies and IgG anti S antibody were found in the serum of this patient. 【Conclusion】 When a patient is found to have cold autoantibodies, it is necessary to screen the alloantibody, in order to avoid post transfusion immune reactions due to missed detection of alloantibody.

Voltage-gated potassium channel-complex antibodies associated clinical syndromes with myasthenia gravis complicated with thymoma: analysis of 2 cases and literature review / 中华神经科杂志

Objective:To investigate the clinical characteristics and outcome of patients with voltage-gated potassium channel complex (VGKCc) antibody associated clinical syndromes complicated with myasthenia gravis (MG) with thymoma.Methods:The clinical history, examinations and follow-up prognosis of 2 cases of VGKCc antibodies associated clinical syndromes with MG complicated with thymoma in Qilu Hospital (Qingdao), Cheeloo College of Medicine,Shandong University in September 2020 and December 2020 were reviewed. Related literatures were summarized at the same time.Results:Case 1, a 64-year-old female clinically presented with cognitive impairment, psychosis, and epilepsy seizures, whose serum autoimmune antibody testing showed positive leucine-rich glioma-inhibited 1 (LGI1) antibody, was diagnosed as anti-LGI1 encephalitis,and had history of MG with thymoma. Her symptoms were improved by immunotherapy. Case 2, a 67-year-old male, was diagnosed as MG, and developed cognitive impairment, myokymia and autonomic dysfunction later. His serum autoimmune antibody testing showed positive contactin associated protein-like 2 antibody. Therefore, Morvan syndrome complicated with MG with thymoma was definitely diagnosed. After admission, the patient was improved with immunotherapy and thymoma resection.Conclusions:Patients with VGKCc antibody-associated clinical syndromes complicated with MG have the clinical characteristics of the two diseases simultaneously, and there is also crossover. Immunotherapy and treatment for thymoma are generally effective.

A clinical analysis of 74 cases of bullous pemphigoid with stroke / 中华皮肤科杂志

Objective:To investigate differences in clinical characteristics between bullous pemphigoid (BP) patients with stroke and those without, and their relationship with the prognosis of stroke.Methods:A retrospective analysis was performed on medical records of 330 BP inpatients in the First Affiliated Hospital of Zhengzhou University from September 2012 to April 2020. These patients were divided into BP + stroke (ST) group and BP - ST group according to whether they were accompanied by stroke, and clinical manifestations and relevant laboratory examination results were compared between the two groups. According to the stroke outcome score assessed by modified Rankin Scale (mRS), patients in the BP + ST group were further divided into good-prognosis ST group (mRS ≤ 2 points) and poor-prognosis ST group (mRS > 2 points), and subgroup analysis was conducted. Correlations between measurement data (such as age, disease course and laboratory examination results) and mRS scores were analyzed.Results:In the BP - ST group (256 cases), 151 were males and 105 were females, and their age ranged from 19 to 92 (66.8 ± 13.6) years; in the BP + ST group (74 cases), 45 were males and 29 were females, and their age ranged from 48 to 92 (74.6 ± 9.6) years; Compared with the BP - ST group, the BP + ST group showed older age ( t = -5.57, P < 0.001), shorter disease course of BP ( Z = -3.07, P = 0.002), and higher anti-BP180 IgG antibody levels (215.0 [157.2, 283.1] U/ml vs. 155.0 [63.9, 279.8] U/ml; Z = -2.12, P = 0.034). The distribution of skin lesions significantly differed between the two groups ( χ2 = 10.51, P = 0.015), and the BP + ST group showed a significantly lower proportion of patients with generalized lesions ( P<0.05), but a higher proportion of patients with lesions on the limbs ( P<0.05). Subgroup analysis showed significant differences in the patients′ age, BP course, lesion distribution and anti-BP180 IgG antibody levels among the good-prognosis ST group, poor-prognosis ST group and BP - ST group ( F = 10.83, P<0.001; Z = 17.24, P<0.001; χ2 = 15.57, P = 0.026; Z = 6.29, P = 0.043, respectively). There was no significant difference in the age between the good-prognosis ST group and poor-prognosis ST group (adjusted P = 1.000), but the patients were significantly older in the two above groups than in the BP - ST group (adjusted P = 0.001, 0.007, respectively) ; the poor-prognosis ST group showed significantly shorter BP courses (adjusted P = 0.016, < 0.001, respectively) and a higher proportion of patients with lesions on the limbs (both P < 0.05) compared with the good-prognosis ST group and BP - ST group, and significantly higher serum anti-BP180 IgG antibody levels compared with the BP - ST group (226.2 [163.6, 285.8] U/ml vs. 155.0 [63.9, 279.8] U/ml; adjusted P = 0.037). There were no significant differences in the gender distribution, lesional morphology, percentages and counts of peripheral blood eosinophils, serum total IgE levels, and anti-BP230 IgG antibody levels between the BP + ST group and BP - ST group (all P > 0.05), or among the good-prognosis ST group, poor-prognosis ST group and BP - ST group (all P > 0.05). Correlation analysis in the BP + ST group showed a significantly negative correlation between the BP course and mRS scores ( r = -0.33, P = 0.004), and a significantly positive correlation between the anti-BP180 IgG antibody levels and mRS scores ( r = 0.34, P = 0.032) . Conclusion:There were differences in the patients′ age, BP course, lesion distribution, and anti-BP180 IgG antibody levels between the BP patients with stroke and those without, and the differences were more obvious between the poor-prognosis ST group and BP - ST group.

Application of the Chinese Expert Consensus on Diabetes Classification in clinical practice / 中华内科杂志

Objective:To evaluate the diagnostic for classification of newly diagnosed diabetes patients and assess the application of the screening tests recommended by the 2022 Chinese Expert Consensus on Diabetes Classification.Methods:Retrospective case series study. The data from the electronic medical record system of patients with new-onset diabetes mellitus (within 1 year of disease onset) who attending the Diabetes Specialist Outpatient Clinic at the Second Xiangya Hospital of Central South University from January 1, 2018 to December 31, 2021 were collected for the analysis. Based on the consensus, patients were categorized according their age of onset, body mass index (BMI), and suspicion of type 1 diabetes mellitus (T1DM). The chi-square statistic was used to compare key classifier indicators, including C-peptide, islet autoantibodies, and genetic markers, in the subgroups. The diagnosis in suspected T1DM patients was also evaluated. The screening strategy recommended in the consensus was further assessed using a logistic regression model and the area under the receiver-operating curve (AUC).Results:A total of 3 384 patients with new-onset diabetes were included. The average age of disease onset was (46.3±13.9) years, and 61.0% (2 065/3 384) of the patients were male. The proportions of patients who completed C-peptide and glutamic acid decarboxylase antibody (GADA) tests were 36.6% (1 238/3 384) and 37.5% (1 269/3 384), respectively. There were no significant differences in C-peptide test results among the subgroups (all P>0.05). In contrast, the GADA detection rate was higher in patients with young age of onset (<30 years old), in those who were non-obese (BMI<24 kg/m 2), and in those clinically suspected of T1DM (all P<0.05). According to the diagnostic pathway proposed by the consensus, only 57.4% (1 941/3 384) of patients could be subtyped. For a definitive diagnosis, the remaining patients needed completion of C-peptide, islet autoantibody, genetic testing, or follow-up. Furthermore, among patients with clinical features of suspected T1DM, the antibody positivity rate was higher than in non-suspected T1DM patients [24.5% (154/628) vs. 7.1% (46/646), P<0.001]. When the clinical features of suspected T1DM defined in the consensus were taken as independent variables and antibody positivity was considered the outcome variable in the logistic regression model, young onset, non-obese onset, and ketosis onset could enter the model. Based on AUC analysis, the accuracy of the diagnostic model was 0.77 (95% CI 0.73-0.81), suggesting that the clinical features of suspected T1DM in the consensus have good clinical diagnostic value for this patient subgroup. Conclusions:There was a significant discrepancy between the clinical practice of diabetes classification and the process recommended by the consensus, which was specifically reflected in the low proportions of both subtyping indicator testing and definitively subtyped diabetes patients. Attention should be pay to the classification diagnosis process proposed in the consensus and the clinical detection rate of key diabetes subtyping indicators such as C-peptide and islet autoantibodies for diabetes classification should be improved. Noteworthy, the screening strategy for T1DM proposed by the consensus showed good clinical application value.

Research progress of juvenile dermatomyositis with anti-melanoma differentiation-associated gene 5 antibody / 中华实用儿科临床杂志

Juvenile dermatomyositis (JDM) is the most common subtype of juvenile idiopathic inflammatory myopathy (JIIM), characterized by non-suppurative inflammation of skin and muscle.JDM frequently involves important organs such as lungs.JDM with anti-melanoma differentiation-associated gene (MDA) 5 antibody has unique clinical characteristics, mainly including skin mucosal ulcer, palm papule, hair loss and arthritis.Interstitial lung disease (ILD) is its most serious complication.The levels of serum ferritin, Krebs von den Lungen-6 and interleukin-18 can be used as important indicators of disease activity and prognosis.Glucocorticoids combined with immunosuppressants are the basic treatment for the disease.Immunosuppressants include calcineurin inhibitors (Cyclosporine A and Tacrolimus), Cyclophosphamide, Azathioprine, Mycophenolate Mofetil, etc.Refractory patients can also be treated with Rituximab, Janus kinase inhibitor and human immunoglobulin.Early active treatment of JDM with anti-MDA 5 antibody can alleviate the symptoms, reverse organ damage and improve the long-term prognosis.

Meta-analysis of Effect of Tripterygium wilfordii Polyglycoside Tablets Combined with Methotrexate and/or Leflunomide on Autoantibodies in Rheumatoid Arthritis / 中国实验方剂学杂志

ObjectiveTo evaluate the effect of Tripterygium wilfordii polyglycoside tablets （TWPT） combined with conventional synthetic disease-modifying antirheumatic drugs （csDMARDs） including methotrexate （MTX） and/or leflunomide （LEF） on autoantibodies in rheumatoid arthritis （RA） patients. MethodPubMed， EMBASE， Web of Science， Cochrane Library， China National Knowledge Infrastructure （CNKI）， VIP， Wanfang Data， and China Biomedical Literature Service System （SinoMed） were searched for randomized controlled trials （RCTs） of TWPT combined with MTX and/or LEF in the treatment of RA patients from database inception to December 1， 2021. Primary outcome indicators included rheumatoid factor （RF） and anti-citrullinated protein antibody （ACPA）， and secondary outcome indicators included immunoglobulin （IgA， IgG， and IgM） and adverse drug events （ADE）. ResultThirty-one RCTs， involving 2 643 adult patients， were included， including 20 RCTs of TWPT combined with MTX， 10 of TWPT combined with LEF， and one of TWPT combined with MTX and TWPT. The follow-up time ranged from two weeks to 13 months. Compared with csDMARDs alone， TWPT combined with other drugs significantly improved serum RF of RA patients ［SMD=-2.45， 95% CI ［-2.97， -1.93］， P<0.000 01］， anti-CCP ［SMD=-1.41， 95% CI （-2.35， -0.48）， P=0.003］， IgM ［SMD=-1.90， 95% CI （-3.03， -0.76）， P=0.001］， and IgA ［SMD=-1.18， 95% CI （-2.23， -0.12）， P=0.03］. There were no significant effects on IgG ［SMD=-1.02， 95% CI （-2.04， 0.01）， P=0.05］ and ADE ［RR=0.87， 95% CI （0.66， 1.15）， P=0.32］. ConclusionThe results of this study show that compared with csDMARDs alone， TWPT combined with csDMARDs can effectively improve the levels of autoantibodies in RA patients without increasing the incidence of ADE. However， due to the limited quality and quantity of the included RCTs， the relevant conclusions are only used as a reference for the clinical diagnosis and treatment of RA， and more high-quality studies are still needed to further confirm their efficacy.

Manifestaciones clínicas "no criterio" del Síndrome Antifosfolipídico. Presentación de una cohorte nacional

Introducción: El síndrome antifosfolipídico (SAF) es una afección de origen autoinmune caracterizada por trombosis, pérdidas fetales recurrentes y anticuerpos antifosfolipídicos (aFL). Existen manifestaciones clínicas no contempladas en los criterios clasificatorios, que se denominan manifestaciones no criterio. Objetivo: Analizar las manifestaciones clínicas del SAF, enfatizando las manifestaciones no criterio y su relación con el perfil de autoanticuerpos en un hospital general de Montevideo, Uruguay. Métodos: Se realizó un estudio retrospectivo de las historias clínicas de pacientes con diagnóstico definitivo o sospecha de SAF en un servicio de medicina ambulatoria de enfermedades autoinmunes, en el Hospital Maciel, asistidos entre el 2010 y 2019. Resultados: Se incluyeron 78 pacientes, con edad media de 50,3 ± 14,5 años, 69 (88,5%) correspondió a sexo femenino. Cuarenta y seis (59,0%) pacientes presentaron SAF secundario, de los cuales 28 (35,9%) asociaron LES. La trombosis venosa de miembros inferiores fue la manifestación más frecuente (51,3%). Dieciocho (24,0%) pacientes presentaron trombosis arteriales en forma de accidente cerebrovascular. Cincuenta y nueve (75.6%) casos presentaron, además de las manifestaciones clasificatorias, alguna de las manifestaciones "no criterio" y éstas se manifestaron de forma aislada en 10 (12.8%) pacientes. Las manifestaciones no clasificatorias más frecuentes fueron artralgias, livedo reticularis, migraña y trombocitopenia. Se observó una asociación significativa entre la presencia de anti-ß2GPI con manifestaciones cutáneas y de trombocitopenia con al menos una manifestación trombótica. Conclusiones: Las manifestaciones "no criterio" del SAF se presentaron en casi 3 de cada 4 casos, frecuencia similar a la observada en otras series. La presencia aislada de manifestaciones "no criterio" podrían hacer sospechar un SAF y en algunos casos, conducir a la solicitud de anticuerpos.

Introduction: Antiphospholipid syndrome (APS) is an autoimmune condition characterized by thrombosis, recurrent fetal loss, and antiphospholipid antibodies. There are clinical manifestations not contemplated in the classification criteria, which are called non-criterion manifestations. Objective: To analyze the clinical manifestations of APS, emphasizing the non-criterion manifestations and their relationship with the autoantibody profile in a general hospital in Montevideo, Uruguay. Methods: A retrospective analysis of the medical records of patients with a definitive or suspected diagnosis of APS in an outpatient medicine service for autoimmune diseases, at the Maciel Hospital, assisted between 2010 and 2019, was carried out. Results: 78 patients were included, with a mean age of 50.3 +/- 14.5 years, 69 (88.5%) were female. Forty-six (59.0%) patients presented secondary APS, of which 28 (35.9%) associated SLE. Venous thrombosis of the lower limbs was the most frequent manifestation (51.3%). Eighteen (24.0%) patients presented arterial thrombosis in the form of cerebrovascular accident. Fifty-nine (75.6%) cases presented, in addition to the classification manifestations, some of the "non-criterion" manifestations and these manifested in an isolated way in 10 (12.8%) patients. The most frequent non-classifying manifestations were arthralgia, livedo reticularis, migraine and thrombocytopenia. A significant association was observed between the presence of anti-ß2GPI with cutaneous manifestations and thrombocytopenia with at least one thrombotic manifestation. Conclusions: Non-criterion manifestations of APS occurred in almost 3 out of 4 cases, a frequency similar to that observed in other series. The isolated presence of "non-criterion" manifestations could lead to suspicion of APS and, in some cases, lead to the request for antibodies.

Introdução: A síndrome antifosfolipídica (SAF) é uma doença de origem auto-imune caracterizada por trombose, perdas fetais recorrentes e anticorpos antifosfolípidos (aFL). Existem manifestações clínicas não abrangidas pelos critérios de classificação, que são designadas por manifestações não-critério. Objetivo: Analisar as manifestações clínicas da SAF, enfatizando as manifestações não-critério e sua relação com o perfil de auto-anticorpos em um hospital geral de Montevidéu, Uruguai. Métodos: Foi realizado um estudo retrospectivo dos prontuários de pacientes com diagnóstico definitivo ou suspeita de SAF em um serviço ambulatorial de doenças autoimunes do Hospital Maciel, atendidos entre 2010 e 2019. Resultados: Foram incluídos 78 pacientes, com idade média de 50,3 +/- 14,5 anos, sendo 69 (88,5%) do sexo feminino. Quarenta e seis (59,0%) pacientes apresentavam PFS secundária, dos quais 28 (35,9%) tinham LES associado. A trombose venosa dos membros inferiores foi a manifestação mais frequente (51,3%). Dezoito (24,0%) doentes apresentaram trombose arterial sob a forma de acidente vascular cerebral. Cinquenta e nove (75,6%) casos apresentaram, para além das manifestações classificatórias, algumas das manifestações "não-critério" e estas manifestações foram isoladas em 10 (12,8%) doentes. As manifestações não classificatórias mais frequentes foram artralgias, livedo reticularis, enxaqueca e trombocitopenia. Foi observada uma associação significativa entre a presença de anti-ß2GPI com manifestações cutâneas e trombocitopenia com pelo menos uma manifestação trombótica. Conclusões: As manifestações "não-critério" de SAF ocorreram em quase 3 de cada 4 casos, frequência semelhante à observada noutras séries. A presença isolada de manifestações "não-critério" pode levantar a suspeita de SAF e, nalguns casos, levar à pesquisa de anticorpos.

Anemia hemolítica autoinmune: mecanismos de inducción de autoinmunidad e inmunobiología / Autoimmune hemolytic anemia: mechanisms of autoimmunity induction and immunobiology

Introducción: La patogénesis de la anemia hemolítica autoinmune es un proceso complejo en el que muchos elementos tienen una función esencial que repercuten en la gran heterogeneidad clínica de la enfermedad, pero los mecanismos involucrados en su inducción se desconocen en gran medida. Objetivo: Explicar los principales mecanismos propuestos en el inicio y aparición de la anemia hemolítica autoinmune y su contribución a la fisiopatología de la enfermedad. Métodos: Se realizó una revisión de la literatura en los idiomas inglés y español, de artículos publicados en los últimos 10 años sobre mecanismos propuestos en el inicio de la anemia hemolítica autoinmune. Análisis y síntesis de la información: Los mecanismos propuestos en la inducción de la autoinmunidad contra los eritrocitos incluyen el mimetismo molecular entre antígenos endógenos y antígenos exógenos, el procesamiento desregulado de autoantígenos influenciado por factores adquiridos y la disfunción de los linfocitos B y T. Conclusiones: Los mecanismos propuestos en la aparición de la anemia hemolítica autoinmune brindan información valiosa para mejorar la comprensión de los mecanismos moleculares involucrados y subrayan la complejidad de los fenómenos involucrados en la perdida de la tolerancia hacia los eritrocitos autólogos y el delicado equilibrio entre factores genéticos y ambientales(AU)

Introduction: The pathogenesis of autoimmune hemolytic anemia is a complex process in which many elements play an essential role and have an impact on the great clinical heterogeneity of the disease, but the mechanisms involved in its induction are largely unknown. Objective: To explain the main mechanisms proposed in the initiation and occurrence of autoimmune hemolytic anemia and its contribution to the pathophysiology of the disease. Methods: A review of the literature, in English and Spanish languages, of articles published in the last 10 years on proposed mechanisms in the initiation of autoimmune hemolytic anemia was carried out. Analysis and synthesis of information: Proposed mechanisms for the induction of autoimmunity against erythrocytes include molecular mimicry between endogenous and exogenous antigens, deregulated processing of autoantigens influenced by acquired factors, and B and T cells dysfunction. Conclusions: The proposed mechanisms in the occurrence of autoimmune hemolytic anemia provide valuable information to improve the understanding of the mechanisms involved and underline the complexity of the phenomena involved in the loss of tolerance towards autologous erythrocytes and the delicate balance between genetic and environmental factors(AU)

Caracterización fisiopatológica de las anemias hemolíticas autoinmunes / Pathophysiological characterization of autoimmune hemolytic anemia

Introducción: La anemia hemolítica autoinmune se define como el aumento de la destrucción de los eritrocitos en presencia de autoanticuerpos dirigidos contra antígenos de grupos sanguíneos eritrocitarios. Objetivo: Caracterizar las anemias hemolíticas autoinmunes teniendo en cuenta las características fisiopatológicas, manifestaciones clínicas y el diagnóstico de laboratorio. Métodos: Se realizó una revisión de la literatura en inglés y español de artículos publicados en los últimos 10 años sobre anemia hemolítica autoinmune. Conclusiones: La anemia hemolítica autoinmune es una enfermedad muy heterogénea. El diagnóstico suele ser fácil, pero los casos difíciles pueden ser un desafío. La definición de cada tipo es fundamental ya que la terapia es diferente y se enfoca más con la comprensión de los mecanismos patogénicos(AU)

Introduction: Autoimmune hemolytic anemia is defined as increased destruction of red blood cells in the presence of autoantibodies directed against red cell blood group antigens. Objective: To characterize autoimmune hemolytic anemias, taking into account immunohematological, clinical, diagnostic and pathogenic mechanisms. Methods: A review of the literature, in English and Spanish, of articles published in the last 10 years on autoimmune hemolytic anemia was carried out. Conclusions: Autoimmune hemolytic anemia is a very heterogeneous disease. Diagnosis is usually easy, but difficult cases can be challenging. The definition of each type is fundamental since the therapy is different and focuses more on understanding the pathogenic mechanisms(AU)

Manifestaciones autoinmunes asociadas a la enfermedad por coronavirus 2019 / Autoimmune manifestations associated with coronavirus disease 2019

Introducción: La enfermedad por coronavirus 2019 (Coronavirus Disease 2019 o COVID-19), causada por un nuevo coronavirus: el síndrome respiratorio agudo severo 2 (severe acute respiratory syndrome coronavirus 2), ha teniendo un impacto devastador en todo el mundo. Su fisiopatología es el resultado de los efectos citopáticos directos del SARS-CoV-2 sobre el epitelio respiratorio, el endotelio y otros tipos de células específicas de órganos, con la posterior inducción de una tormenta de citocinas proinflamatorias y una inmunidad adaptativa desregulada que causa daño tisular severo. Objetivo: Describir las características autoinmunes presentes durante la infección por SARS-CoV-2. Métodos: Se realizó una revisión bibliográfica sobre COVID-19 y manifestaciones autoinmunes en los sitios web: Pubmed, Medline, SciELO. Se hizo un análisis y resumen de la información revisada. Análisis y síntesis de la información: Los virus se han considerado los principales agentes infecciosos que desencadenan fenómenos autoinmunes en individuos genéticamente susceptibles. El SARS-CoV-2 ya se ha relacionado con una larga lista de afecciones autoinflamatorias y autoinmunes que pueden ser inducidas por varios mecanismos propuestos para explicar la autoinmunidad inducida por virus. En esta patología, el más descrito, es el mimetismo molecular. La COVID-19 comparte similitudes con las enfermedades autoinmunes en sus manifestaciones clínicas, mecanismos fisiopatológicos y respuesta terapéutica, de forma que potentes reacciones inmunes participan en la patogénesis de ambas enfermedades. Conclusiones: La infección por SARS-CoV-2 puede representar al vínculo complejo e interrelacionado entre las infecciones y la autoinmunidad(AU)

Introduction: Coronavirus disease 2019 (COVID-19), caused by a new coronavirus. Severe acute respiratory syndrome coronavirus 2 is having a devastating impact throughout the world. Its pathophysiology is the result of direct cytopathic effects of SARS-CoV-2 on respiratory epithelium, endothelium, other organ-specific cell types and the subsequent induction of a pro-inflammatory cytokine storm and dysregulated adaptive immunity, causing severe tissue damage. Objective: To describe autoimmune characteristics present during SARS-Cov-2 infection. Methods: A literature review on COVID-19 and autoimmune manifestations was carried out. The articles were selected from a search of the following websites: Pubmed, Medline, SciELO. An analysis and summary of the reviewed information was made. Analysis and synthesis of information: Viruses have been considered the main infectious agents that trigger autoimmune phenomena in genetically susceptible individuals. SARS-CoV-2 has already been linked to a long list of autoinflammatory and autoimmune conditions that can be induced by various mechanisms proposed to explain virus-induced autoimmunity. In this pathology, the most described, is molecular mimicry. COVID-19 shares similarities with autoimmune diseases in its clinical manifestations, pathophysiological mechanisms and therapeutic response, such powerful immune reactions participate in the pathogenesis of both entities. Conclusions: SARS-CoV-2 infection may represent the complex and interrelated link between infections and autoimmunity(AU)

Guía práctica para la solicitud de marcadores humorales de autoinmunidad y estudios genéticos en diabetes mellitus / A practical guide to request humoral autoimmunity markers and genetic tests in diabetes mellitus

La diabetes mellitus (DM) es una enfermedad heterogénea que presenta fenotipos clínicos diversos, todos con hiperglucemia. Históricamente se han utilizado cuatro factores para identificar esta diversidad: la edad de inicio, la gravedad de la enfermedad o grado de pérdida de la función de la célula beta, el grado de resistencia a la insulina y la presencia de autoanticuerpos asociados a la enfermedad. Actualmente, los parámetros empleados para clasificar los diferentes tipos de DM dificultan el diagnóstico y tratamiento de los pacientes. Las distintas presentaciones clínicas requieren una clasificación diagnóstica más eficaz para un abordaje terapéutico más preciso, valiéndose del avance de la inmunogenética y la bioquímica clínica. Esta guía está orientada a clasificar con precisión las presentaciones clínicas que a menudo generan incertidumbre dentro de los dos tipos principales de DM.

Diabetes mellitus (DM) is a heterogeneous disease, with diverse clinical phenotypes, all with hyperglycemia. Historically, four factors have been used to identify this diversity: the age at onset, the severity of the disease, that is, the degree of loss of beta cell function and insulin resistance, and the presence of circulating autoantibodies. Currently, the parameters used to classify the different types of DM make it difficult to diagnose and treat patients. The different clinical manifestations require an accurate diagnosis to achieve an effective therapeutic approach through the use of immunogenetics and clinical biochemistry. This practical guide aims to accurately classify the often uncertain clinical presentations within the two main types of diabetes.

Autoanticuerpos anti-insulina en la diabetes tipo 1 / Anti-insulin autoantibodies in type 1 diabetes

Introducción: Los autoanticuerpos anti-insulina (AAI) representan un marcador serológico de la diabetes tipo 1 (DT1). El significado clínico de los AAI aún no ha sido determinado en la población cubana. Objetivo: Determinar el valor clínico de AAI en pacientes con DT1. Métodos: Se determinaron los niveles séricos de AAI por el ensayo inmuno-adsorbente ligado a enzima (ELISA) en 33 pacientes adultos con DT1, 78 pacientes con otras condiciones endocrinas (CEE) como diabetes tipo 2, tiroiditis de Hashimoto e hiperinsulinemia, y 49 controles normales (CN). El valor de corte se determinó con el análisis de las curvas características operativas del receptor (COR) (ROC por sus siglas en inglés). Se utilizaron pruebas no paramétricas para comparar los niveles de AAI de pacientes con DT1, CEE y CN, y determinar la correlación entre AAI y la edad. Resultados: El valor de corte óptimo de AAI para DT1 fue el índice de 1,05, con sensibilidad de 45,5 por ciento, especificidad de 81,6 por ciento, razón de verosimilitud positiva de 2,47, y razón de verosimilitud negativa de 0,67. Los niveles de AAI en DT1 (índice de 0,97) fueron significativo, más altos que los de CN (índice de 0,70; p=0,020) y los de CEE (índice de 0,63; p= 0,009). Los niveles de AAI resultaron inversamente proporcionales a la edad en pacientes diabéticos ( =-0,252; p=0,030). Conclusiones: Los pacientes con DT1 se distinguieron por niveles más altos de AAI, aunque la presencia de estos anticuerpos no fue exclusiva de DT1. Los niveles de AAI dependieron de la edad en los pacientes diabéticos(AU)

Introduction: Anti-insulin autoantibodies (AAI) represent a serological marker of type 1 diabetes (T1D). The clinical significance of AAIs has not yet been determined in the Cuban population. Objective: To determine the clinical value of AAI in patients with T1D. Methods: AAI serum levels were determined by enzyme-linked immunosorbent assay (ELISA) in 33 adult patients with T1D, 78 patients with other endocrine conditions (CEE) such as type 2 diabetes, Hashimoto's thyroiditis, and hyperinsulinemia, and 49 normal controls (CN). The cut-off value was determined by receiver operating characteristic (ROC) curve analysis. Nonparametric tests were used to compare the AAI levels of patients with T1D, CEE, and CN, and to determine the correlation between AAI and age. Results: AAI optimal cut-off value for T1D was the index of 1.05, with 45.5 percent of sensitivity, 81.6 percent specificity, 2.47 positive likelihood ratio, and 0.67 negative likelihood ratio. AAI levels in DT1 (index of 0.97) were significant, higher than those of CN (index of 0.70; p= 0.020) and CEE levels (index of 0.63; p= 0.009). AAI levels were inversely proportional to age in diabetic patients (ρ = -0.252; p=0.030). Conclusions: Patients with T1D were distinguished by AAI higher levels, although the presence of these antibodies was not exclusive to T1D. AAI levels depended on age in diabetic patients(AU)