HLA-B27 did not protect against COVID-19 in patients with axial spondyloarthritis - data from the ReumaCov-Brasil Registry

Abstract Background Some studies have suggested the HLA-B27 gene may protect against some infections, as well as it could play a benefit role on the viral clearance, including hepatitis C and HIV. However, there is lack of SARS-CoV-2 pandemic data in spondyloarthritis (SpA) patients. Aim To evaluate the impact of HLA-B27 gene positivity on the susceptibility and severity of COVID-19 and disease activity in axial SpA patients. Methods The ReumaCoV-Brasil is a multicenter, observational, prospective cohort designed to monitor immunemediated rheumatic diseases patients during SARS-CoV-2 pandemic in Brazil. Axial SpA patients, according to the ASAS classification criteria (2009), and only those with known HLA-B27 status, were included in this ReumaCov-Brasil's subanalysis. After pairing them to sex and age, they were divided in two groups: with (cases) and without (control group) COVID-19 diagnosis. Other immunodeficiency diseases, past organ or bone marrow transplantation, neoplasms and current chemotherapy were excluded. Demographic data, managing of COVID-19 (diagnosis, treatment, and outcomes, including hospitalization, mechanical ventilation, and death), comorbidities, clinical details (disease activity and concomitant medication) were collected using the Research Electronic Data Capture (REDCap) database. Data are presented as descriptive analysis and multiple regression models, using SPSS program, version 20. P level was set as 5%. Results From May 24th, 2020 to Jan 24th, 2021, a total of 153 axial SpA patients were included, of whom 85 (55.5%) with COVID-19 and 68 (44.4%) without COVID-19. Most of them were men (N = 92; 60.1%) with mean age of 44.0 ± 11.1 years and long-term disease (11.7 ± 9.9 years). Regarding the HLA-B27 status, 112 (73.2%) patients tested positive. There were no significant statistical differences concerning social distancing, smoking, BMI (body mass index), waist circumference and comorbidities. Regarding biological DMARDs, 110 (71.8%) were on TNF inhibitors and 14 (9.15%) on IL-17 antagonists. Comparing those patients with and without COVID-19, the HLA-B27 positivity was not different between groups (n = 64, 75.3% vs. n = 48, 48%, respectively; p = 0.514). In addition, disease activity was similar before and after the infection. Interestingly, no new episodes of arthritis, enthesitis or extra-musculoskeletal manifestations were reported after the COVID-19. The mean time from the first symptoms to hospitalization was 7.1 ± 3.4 days, and although the number of hospitalization days was numerically higher in the B27 positive group, no statistically significant difference was observed (5.7 ± 4.11 for B27 negative patients and 13.5 ± 14.8 for B27 positive patients; p = 0.594). Only one HLA-B27 negative patient died. No significant difference was found regarding concomitant medications, including conventional or biologic DMARDs between the groups. Conclusions No significant difference of COVID-19 frequency rate was observed in patients with axial SpA regarding the HLA-B27 positivity, suggesting a lack of protective effect with SARS-CoV-2 infection. In addition, the disease activity was similar before and after the infection. Trial registration This study was approved by the Brazilian Committee of Ethics in Human Research (CONEP), CAAE 30186820.2.1001.8807, and was registered at the Brazilian Registry of Clinical Trials - REBEC, RBR-33YTQC. All patients read and signed the informed consent form before inclusion.

HLA-B27 positivity in a large miscegenated population of 5,389,143 healthy blood marrow donors in Brazil

Abstract Background The prevalence of HLA-B27 gene positivity in healthy Caucasian communities varies between 8 and 14%. However, there is a lack of information in countries with a high rate of miscegenation, such as Brazil. Aim To estimate the frequency of HLA-B27 in the Brazilian general population using a large national registry database. Methods This is a cross-sectional ecological study using the Brazilian Registry of Volunteer Bone Marrow Donors (REDOME) database on HLA-B27 allelic frequency and proportion of positives of healthy donors (18-60 years old). Data were analyzed according to sex, age, race (by self-reported skin color recommended by the Brazilian Institute of Geography and Statistics - IBGE), and geographic region of residence. Results From 1994 to 2022, a total of 5,389,143 healthy bone marrow donors were included. The overall positivity for HLA-B27 was 4.35% (CI 95% 4.32-4.37%), regardless of sex and age (57.2% were women, mean age was 41.7yo). However, there was a difference between races: 4.85% in Whites; 2.92% in Blacks; 3.76% in Pardos (Browns i.e. mixed races); 3.95% in Amarelos (Yellows i.e. Asian Brazilians); and 3.18% in Indigenous. There was also a difference regarding geographic region of residence (North: 3.62%; Northeast: 3.63%; Southeast: 4.29%; Midwest: 4.5% and 5.25% in South). The homozygosity rate for the HLA-B27 was 1.32% of all the positives and only 0.06% in the general population. Conclusions Our findings provide the first Brazilian national prevalence for HLA-B27 in 4.35%. There is a gradient gene positivity from North to South, suggesting that the genetic background related to the miscegenation due to colonization, slavery, and some later waves of immigration together with internal migratory flows, could explain our findings.

A STUDY OF CLINICAL AND ETIOLOGICAL PATTERN AND SEASONAL VARIATION IN THE INCIDENCE OF ANTERIOR UVEITIS AT A TERTIARY CARE CENTER

Purpose: The aim was to study the various pattern and any seasonal variation in the incidence of anterior uveitis at a tertiary care center. An observational study was conducted on 100 patients of all Methods: new uveitis cases who attended the OPD between January 2020 to December 2021 of a tertiary care center, J.L.N. medical college and hospital, Ajmer, Rajasthan. We grouped the months into winter, autumn, monsoon, spring and summer according to Indian weather. Cases were screened along with detailed clinical and laboratory investigation to ?nd out there clinical etiological causes. 100 Patients of uveitis were examined. There was male predominance (66%) with male to female Result: ratio 1.94:1. We found cases with unilateral (91%) uveitis to be more common, with more Right eye (48%) involvement. Majority (40%) of cases remained idiopathic. HLA-B27 (37%) was commonest association followed by lens induced and Tuberculosis. The incidence of uveitis in winter season (38%) followed by 33% in transitional season and 29% in summer. Non- Conclusion: infectious uveitis were more common. In Non-infectious uveitis, most common entity found to be Idiopathic and HLA-B27 associated whereas in infectious uveitis, ocular tuberculosis was found to be the leading cause. Seasonally uveitis were more in winter and less in summer

Intestinal Behcet’s : A Rare Presentation of Behcet’s Disease

We herein present a case of 48 years old female patient presented with fever, bloody diarrhea followed by palpable purpuric rash over the body along with recurrent oral and genital ulceration. These were associated with history of symmetric polyarthralgia. On examination moderate anemia, signs of anterior uveitis were found. In blood parameters thrombocytopenia along with elevated Erythrocyte Sedimentation Rate, C-Reactive Protein were noted. On further investigations the serological tests were found to be negative for Dengue, Chikungunya, HIV, HBV, HCV. Complement C3 found to be low. Colonoscopic biopsy is diagnostic of Indeterminate Crohn’s Disease with IgA, G, M, C3, Fibrinogen immunostaining in skin biopsy. ANA, P-ANCA, C-ANCA were found to be nonreactive for the patient. All of the above mentioned points were pointing towards Behcet’s disease. For confirmation, Anti Saccharomyces Cerevisae Antibody was found to be positive . Skin pathergy test was positive. So, we diagnosed this case as behcet’s disease.

Spondyloarthritis: Characterization of a cohort. Pablo Tobón Uribe Hospital. Medellín, Colombia / Espondiloartritis: caracterización de la cohorte del Hospital Pablo Tobón Uribe, Medellín, Colombia

ABSTRACT Introduction: Spondyloarthritis is a group of chronic inflammatory diseases. Several factors of the disease remain unknown, including clinical and radiological behavior, the demographic characteristics and burden of disease in Colombian patients. Objective: To characterize the demographic aspects, the clinical and paraclinical behaviour, and the therapeutic requirements of a cohort of patients with spondyloarthritis followed-up in the Hospital Pablo Tobón Uribe from January 1, 2005 to December 31, 2017. Methodology: Cohort study. The population was characteriszed using descriptive statistics, qualitative variables using simple and relative frequencies, and quantitative variables using means and standard deviation or medians with their interquartile ranges. Results: The cohort consisted of 181 patients, 100 men (54.9%) and 81 women (44.5%). Just under one half (45.1%) had ankylosing spondylitis, 18.1% undifferentiated spondyloarthritis, 17.1% psoriatic arthropathy, 14.8% reactive arthritis, and 4.4% inflammatory bowel disease. More than two-thirds (69.8%) of the patients had peripheral manifestations, and 67% had axial. A positive HLAB27 was observed in 55.6% of patients. The MRI showed acute and chronic changes in the sacroiliac in 69% and 37%, respectively, with radiological sacroiliitis being observed in 59.5% of cases. The large majority (91.1%) of the patients were treated with PII of original article: S0121-8123(21)00018-9 NSAIDs, 60.1% with sulfasalazine, 43.4% with COX2 inhibitors, and 33.7% with methotrexate. TNFa inhibitors were required by 56.6% of the subjects 3 years after the onset of symptoms. The most commonly used biological drugs were Adalimumab (31.1%), etanercept (21.7%), infliximab (13.1%), golimumab 6.1%, and certolizumab 0.5%. Conclusions: Ourpopulation was characterized by a high activity and functional compromise demonstrated by the high scores of BASDAI and BASFI, and because 56.6% of the patients required anti-TNFa agents.

RESUMEN Introducción: Las espondiloartritis son un grupo de enfermedades inflamatorias crónicas. Se desconoce su comportamiento en nuestro medio, al igual que el comportamiento clínico y radiológico, las características demográficas y la carga de enfermedad en los pacientes colombianos. Objetivos: Caracterizar los aspectos demográficos, el comportamiento clínico y paraclínico y los requerimientos terapéuticos de la cohorte de pacientes con espondiloartritis seguidos en el Hospital Pablo Tobón Uribe desde el 1.° de enero del 2005 hasta el día 31 de diciembre del 2017. Metodología: Estudio de cohorte. La población se caracterizó mediante estadística descrip tiva, las variables cualitativas mediante frecuencias simples y relativas, en tanto que para las cuantitativas se emplearon medias y desviación estándar o medianas con sus rangos intercuartílicos. Resultados: La cohorte está constituida por 181 pacientes, 100 hombres (54,9%) y 81 mujeres (44,5%). El 45,1% tenía espondilitis anquilosante, el 18,1% espondiloartritis indiferenciada, el 17,1% artropatía psoriásica, el 14,8% artritis reactiva y el 4,4% enfermedad inflamatoria intestinal. El 69,8% de los pacientes tenía manifestaciones periféricas y el 67% axiales. El 55,6% de los pacientes tuvo HLAB27 positivo. La RMN mostró cambios agudos y crónicos en las sacroilíacas en el 69% y 37%, respectivamente; en el 59,5% de los casos se observó sacroileítis radiológica. el 91,1% de los pacientes se trató con AINE, el 60,1% con sulfasa lazina, el 43,4% con inhibidores COX2 y el 33,7% con metotrexato. El 56,6% de los sujetos requirió inhibidores-TNFa 3 arios después del inicio de los síntomas. Los biológicos más uti lizados fueron adalimumab (31,1%), etanercept (21,7%), infliximab (13,1%), golumimab (6,1%) y certolizumab (0,5%). Conclusiones: Nuestra población se caracterizó por una alta actividad y gran compromiso funcional, lo que se refleja en altos puntajes de Basdai y Basfi y en que el 56,6% de los pacientes requirió agentes anti-TNFa.

Clinical significance of group A streptococcal infection in pediatric patients with enthesitis related arthritis / 中华风湿病学杂志

Objective:To demonstrate the clinical significance of group A streptococcal infection (GAS) in patients with enthesitis related arthritis (ERA).Methods:A retrospective study was conducted on ERA (136) and PolyRF-/Oligo juvenile idiopathic arthritis (JIA) (272) patients in Beijing Children's Hospital from 2016 to 2018. Anti-streptococcal hemolysin "O" (ASO) was tested and documented in all patients. The infection rate of GAS was compared between patients with ERA and PolyRF-/Oligo JIA. Patients with ERA were divided to two groups according to the result of ASO (ASO positive and ASO negative). All the clinical data were documented and compared within the two groups. The statistical methods used mainly include t test, rank sum test, chi-square test, and Spearman correlation analysis.Results:The GAS infection rate of patients with ERA was higher than patients with PolyRF-/Oligo JIA (17.6% vs 9.5%, χ2=5.52, P=0.019). In ERA patients, clinical data were analyzed, and a statistical significant difference was observed in the presence of human leukocyte antigen (HLA)-B27 between ASO positive and ASO negative group [75.0%(18/24) vs 49.1%(55/112), χ2=5.329, P=0.021]. Statistical differences were found in Patrick's sign positive rate between the two groups [100%(24/24) vs 67.0%(75/112), χ2=10.61, P=0.001]. There was statistically significant difference between the two groups regarding the radiogr-aphic grading at the sacroiliac joint. More patients with positive ASO had grade Ⅲ damage at the sacroiliac joint compare to patients with negative ASO [68.2%(15/22) vs 28.4%(29/102), χ2=12.49, P<0.001]. The logarithmic of the ASO was slightly correlated with the radiographic grade of sacroiliac joint ( r=0.26, P=0.005). Conclusion:Patients with ERA are prone to be infected by GAS. It's probably related to HLA-B27 postivity for antigen presentation. Patients who were infected by GAS fre-quently have sacroiliac joint involvement, and tend to be more sever. This indicates that GAS may play an important role in the pathogenesis of sacroiliac joint destruction.

Expression of inflammatory factors in peripheral blood of patients with HLA-B27 positive and negative uveitis / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To explore the correlation by analyzing and comparing the expression of inflammatory factors in peripheral blood of human leukocyte antigen-B27(HLA-B27)positive and negative uveitis patients.METHODS: All 76 patients first diagnosed with uveitis in our hospital from January 2020 to April 2022 were screened in this retrospective study. Nucleated cells were isolated from human venous blood, and HLA-B27 was detected by flow cytometry(direct immunofluorescence), the patients were divided into the HLA-B27-positive group(≥90%)in 35 cases and HLA-B27-negative group(≤5%)in 41 cases. The whole blood RNA was extracted. The mRNA expression of interleukin-1β(IL-1β), interleukin-6(IL-6), interleukin-10(IL-10), protease activated receptor 2(PAR2), tumor necrosis factor-α(TNF-α), interleukin enhancer-binding factor -3(ILF3)were detected and compared by RT-qPCR.RESULTS: The IL-1β, IL-10, PAR2 and TNF-α mRNA were observed no difference between the two groups of patients(all P&#x003E;0.05). The IL-6 mRNA in the patients of HLA-B27-positive group was higher than in the HLA-B27-negative group, the ILF3 mRNA was lower than that in the negative group(all P&#x003C;0.05).CONCLUSION: The expression level of IL-6 in peripheral blood was significantly increased and ILF3 was decreased in HLA-B27-positive group, which can be used as auxiliary indicators for diagnosis and treatment of HLA-B27-positive uveitis.

Niveles de antitoxina tetánica y diftérica relacionadas con el alelo HLA-B27 en pacientes cubanos con uveítis anterior no infecciosa / Tetanus and diphtheria antitoxin levels related to the HLA-B27 allele in Cuban patients with non-infectious anterior uveitis

La uveítis anterior no infecciosa es una enfermedad inflamatoria del ojo que afecta al tracto uveal y que puede causar ceguera total y otras discapacidades visuales. Esta enfermedad se ubica en el espectro de enfermedades autoinmunes y autoinflamatorias. Se han descrito respuestas no adecuadas a la vacunación en enfermedades mediadas por el sistema inmune, por lo que se evaluaron los niveles de antitoxina tetánica y diftérica en pacientes cubanos con uveítis anterior no infecciosa, relacionada con el alelo HLA-B27. Se determinaron los niveles de antitoxina tetánica y diftérica mediante ELISA en 190 pacientes con uveítis anterior no infecciosa y controles supuestamente sanos. El 97,37 por ciento de los pacientes con uveítis mostraron niveles de protección de antitoxina tetánica mayor o igual a 0,1 UI/mL, similar a lo observado en los controles sanos (98,95 por ciento) (p=0,4385). Las proporciones de pacientes con uveítis anterior no infecciosa y sus controles en los diferentes niveles de protección de antitoxina tetánica fueron similares (p>0,05), al igual que los títulos medios geométricos (p=0,2907). En los pacientes con uveítis, de 65 años o más, se detectó una mayor proporción de individuos con títulos protectores de larga duración (>1,0 UI/mL) de antitoxina diftérica (p=0,0065). En los pacientes con uveítis no se observó asociación entre la presencia del alelo HLA-B27 y la respuesta de anticuerpos frente al toxoide tetánico (p=0,6196) y diftérico (p=0,1917). El 37,9 por ciento de los pacientes con uveítis y el 42 por ciento de los controles, presentaron títulos no protectores (<0,1 UI/mL) de antitoxina diftérica (0,1148). La mayoría de los pacientes con uveítis anterior no infecciosa y los controles supuestamente sanos presentaron protección frente al toxoide tetánico; mientras que, en los pacientes con uveítis, así como en los controles supuestamente sanos, con edad igual o más de 18 años, se debe reevaluar incluir refuerzos con toxoide diftérico para alcanzar mayores niveles de protección frente a la difteria(AU)

Non-infectious anterior uveitis is an inflammatory disease of the eye that affects the uveal tract and can cause total blindness and other visual disabilities. Autoimmune and inflammatory diseases are associated with qualitative and quantitative alterations in the immune response; therefore, the levels of tetanus and diphtheria antitoxin related to the HLA-B27 allele were evaluated in Cuban patients with non-infectious anterior uveitis. Tetanus and diphtheria antitoxin levels were determined by ELISA in 190 patients with non-infectious anterior uveitis and healthy control individuals. 97.37 percent of patients with uveitis showed protective tetanus antitoxin levels greater than and equal to 0.1 IU/mL as well as healthy controls (98.95 percent) (p=0.4385). The proportions of patients with non-infectious anterior uveitis and presumably healthy controls in the different levels of protective tetanus antitoxin were similar (p>0.05) at all levels of protection, as were the geometric mean titers for this antitoxin (p=0.2907). Patients with uveitis aged 65 years or older had a higher proportion of individuals with long-term reliable protective titers (>1.0 IU/mL) of diphtheria antitoxin (p=0.0065). In uveitis patients, no association was observed between the presence of the HLA-B27 allele and the antibody response against tetanus toxoid (p=0.6196) and diphtheria (p=0.1917). Similarly, 37.9 percent of patients with uveitis and 42 percent of their controls had non-protective titers (<0.1 IU/mL) of diphtheria antitoxin (0.1148). Most patients with anterior uveitis and control subjects were protected against tetanus (p>0.05), while in patients with uveitis and supposedly healthy controls, aged 18 years or older, the administration of booster doses with diphtheria toxoid should be reevaluated to achieve higher levels of protection against diphtheria(AU)

Polymorphism analysis of HLA-B alleles in Jiangsu Han population from 8 prefecture-level cities / 中国输血杂志

【Objective】 To investigate the frequencies of HLA-B alleles in Jiangsu Han population from Chinese Marrow Donor Program (CMDP) Jiangsu Branch in 8 prefecture-level cities, compare and analyze the distribution of common susceptible alleles at HLA-B locus in 8 prefecture-level cities. 【Methods】 The HLA-B locus of 27 249 unrelated volunteers from CMDP Jiangsu Branch were genotyped by polymerase chain reaction–sequence based typing (PCR-SBT) method, and frequencies of HLA-B alleles of 8 prefecture-level cities were calculated and compared. 【Results】 A total of 145 HLA-B alleles were detected in Jiangsu Han population, among them 104, 113, 83, 88, 88, 85, 84, 72 HLA-B alleles were detected in Changzhou, Nanjing, Zhenjiang, Yangzhou, Huai’an, Suqian, Xuzhou, and Yancheng Han population, respectively. In general, the common alleles in Changzhou, Yangzhou and Zhenjiang were very similar, and the most common alleles were B*46∶01, 13∶02, 40∶01 and 58∶01. The common alleles in Nanjing, Huai’an and Suqian were rather similar, and the most common alleles were B*13∶02, 46∶01, 40∶01, 58∶01 and 51∶01. The common alleles in Yancheng were rather similar to Nanjing, Huai’an and Suqian, with only difference in the order of B*40∶01 and B*58∶01. The common alleles in Xuzhou were close to Nanjing, Huai’an and Suqian too, with only difference in the order of B*40∶01 and B*46∶01. 【Conclusion】 The results reflected the distribution of HLA-B alleles of Jiangsu Han population from 8 prefecture-level cities and the gene distribution was basically consistent with the regional distribution. The major difference in HLA-B locus in Jiangsu 8 prefecture-level cities was B * 13∶02 and B * 46∶01. The frequency of B * 13∶02 in Northern Jiangsu (Huai’an, Suqian, Xuzhou, Yancheng) is much higher than that of B * 46∶01, and that in Nanjing is slightly higher than the frequency of B * 46∶01, which is consistent with that in North China. The frequency of B * 46∶01 in Southern Jiangsu (Changzhou), Yangzhou and Zhenjiang is higher than that of B * 13∶02, which is consistent with that in South China. The polymorphism analysis of alleles at HLA-B locus in 8 cities in Jiangsu Province provided significant basic data for the study of the correlation between HLA-B locus genes and diseases, as well as the population genetics and anthropology in Jiangsu Han population.

Acometimento vascular na doença de Behçet: o processo imunopatológico / Vascular involvement in Behçet's disease: the immunopathological process

Resumo A doença de Behçet constitui uma forma rara de vasculite sistêmica, que acomete de pequenos a grandes vasos. É caracterizada por manifestações mucocutâneas, pulmonares, cardiovasculares, gastrointestinais e neurológicas. Sua apresentação clínica é bastante ampla, variando de casos mais brandos a casos graves, com acometimento multissistêmico, caracteristicamente com exacerbações e remissões. Suas causas ainda são desconhecidas; entretanto, há evidências genéticas, ambientais e imunológicas, como a associação com o alelo HLA-B51. Todas essas, em conjunto, apontam para um processo imunopatológico anormal, com ativação de células da imunidade inata e adaptativa, como as células natural killer, neutrófilos e células T, que geram padrões de respostas e citocinas específicos capazes de gerar mediadores que podem lesionar e inflamar o sistema vascular, resultando em oclusões venosas, arteriais e/ou formação de aneurismas.

Abstract Behçet's disease is a rare form of systemic vasculitis that affects small to large vessels. It is characterized by mucocutaneous, pulmonary, cardiovascular, gastrointestinal, and neurological manifestations. Its clinical presentation is quite wide, ranging from milder cases to severe cases, with multisystemic involvement, characteristically with exacerbations and remissions. Its etiopathogenesis is still unclear, although there is evidence of genetic, environmental, and immunological factors, such as the association with the HLA-B51 allele. In conjunction, all of these point to an abnormal immunopathological process, with activation of cells of innate and adaptive immunity, such as NK cells, neutrophils, and T cells, which generate specific response patterns and cytokines capable of generating mediators that can damage and inflame blood vessels, resulting in venous and arterial occlusions and/or aneurysm formation.

Agranulocitosis febril y artropatía reactiva asociada a consumo de cocaína en un paciente HLA B27 positivo / Febrile agranulocytosis and reactive arthropathy associated with cocaine consumption in an HLA B27 positive patient

Resumen La agranulocitosis asociada al consumo de cocaína es un fenómeno vinculado a la presencia de levamisol, un agente antihelmíntico e inmunomodulador, usado como adulterante de la cocaína. Esta reacción puede presentarse con mayor frecuencia en personas con HLA B27. Además de la agranulocitosis, las personas que consumen cocaína adulterada con levamisol pueden desarrollar fiebre, lesiones en piel, artralgias y, menos frecuentemente, artritis y entesitis inflamatoria. Presentamos el caso de un paciente consumidor de cocaína, con genotipo HLA B27, que desarrolló agranulocitosis febril y artropatía reactiva. En sangre se detectó la presencia de ANCA p, ANCA atípico y MPO, y fueron excluidas otras causas de agranulocitosis. Fue tratado con corticoides y posteriormente metotrexato, terapia de deshabituación, con buena evolución.

Abstract Agranulocytosis associated with cocaine use is a phenomenon linked to the presence of levamisole, an anthelminthic and immunomodulating agent, used as an adulterant to cocaine. This reaction has been associated with the presence of HLA B27. In addition to agranulocytosis, people who use levamisole-adulterated cocaine may develop fever, skin lesions, arthralgias, and less frequently, inflammatory enthesitis and arthritis. We present the case of a cocaine-consuming patient with HLA B27 genotype, who developed febrile agranulocytosis and inflammatory arthropathy. The presence of p ANCA, atypical ANCA and MPO was detected in blood, and other causes of agranulocytosis were excluded. He was treated with corticosteroids and later methotrexate, therapy for addiction, with good evolution.

Evaluar la calidad de vida y funcionalidad en pacientes con espondilitis anquilosante / Evaluate quality of life and the function in patients with ankylosing spondylitis

INTRODUCCIÓN. La Espondilitis Anquilosante compromete la calidad de vida del pacien-te por tratarse de una enfermedad de afectación axial, ocular, gastrointestinal y articular discapacitante que limita actividades básicas de la vida diaria que repercute en su entorno social. OBJETIVO. Evaluar la calidad de vida, funcionalidad y actividad de la enfermedad en pacientes con Espondilitis Anquilosante. MATERIALES Y MÉTODOS. Estudio trans-versal analítico, con una poblacion de 166 pacientes, una muestra de 120 con diagnós-tico de Espondilitis Anquilosante de la Unidad Técnica de Reumatología del Hospital de Especialidades Carlos Andrade Marín. Se aplicó un cuestionario estructurado que midió la actividad fisica, presencia del Antígeno Leucocitario Humano B-27, se utilizó escalas va-lidadas a nivel internacional que evaluaron calidad de vida, funcionalidad y actividad de la enfermedad. El análisis univariado, bivariado y multivariado, se calculó con Chi-cuadrado y Odds Ratios en el programa estadistico SPSS 23.0. RESULTADOS. Se observó un 50% (60; 120) de ligera afectación en calidad de vida, en funcionalidad el 74,2% (89; 120) pre-sentó afectación mientras que en actividad de la enfermedad en la encuesta Ankylosing Spondylitis Disease Activity Score se encontró actividad alta con un 43,3% (52; 120) y en Bath Ankylosing Spondylitis Disease Activity Index 55% (66; 120) de enfermedad activa. El tratamiento combinado presentó mayor riesgo para afectación en la funcionalidad, en actividad de la enfermedad baja, alta y muy alta con valor p= 0,022; 0,014; 0,026 de forma respectiva. CONCLUSIÓN. La calidad de vida se vio afectado en mujeres y quienes no realizaron actividad física; se encontró comprometido la funcionalidad en quienes recibie-ron tratamiento combinado.

INTRODUCTION. Ankylosing Spondylitis compromises the quality of life of the patient as it is a disease of axial, ocular, gastrointestinal and articular disabling affectation that limits basic activities of daily life that affects the social environment. OBJECTIVE. To evaluate the quality of life, functionality and activity of the disease in patients with Ankylosing Spond-ylitis. MATERIALS AND METHODS. Analytical transversal study, with a population of 166 patients, a sample of 120 with a diagnosis of Ankylosing Spondylitis from the "Unidad Téc-nica de Reumatología del Hospital de Especialidades Carlos Andrade Marín". A structured questionnaire was applied to measure physical activity, presence of Human Leukocyte Antigen B-27, using internationally validated scales that evaluated quality of life, functio-nality and disease activity. Univariate, bivariate and multivariate analysis was calculated with Chi-square and Odds Ratios in the statistical program SPSS 23.0. RESULTS. A 50% (60; 120) of slight affectation in quality of life was observed, in functionality 74,2% (89; 120) presented affectation while in disease activity the Ankylosing Spondylitis Disease Activity Score found high activity with 43,3% (52; 120) and in Bath Ankylosing Spondylitis Disease Activity Index 55% (66; 120) of active disease. Combined treatment presented a greater risk of affecting functionality, low, high and very high disease activity with p values of 0,022; 0,014 and 0,026, respectively. CONCLUSION. Quality of life was affected in women and those who did not carry out physical activity; functionality was found to be compromised in those who received combined treatment.

Flucloxacillin-Induced Hepatotoxicity - Association with HLA-B*5701

SUMMARY Drug-induced liver injury (DILI) to flucloxacillin is rare and is classified as idiosyncratic, as it is dependent on individual susceptibility, unpredictable, and dose-independent. The authors present the case of a 74 - year - old man with a history of monoclonal gammopathy under investigation and alcoholic habits of 24 g/day, with asthenia, anorexia, nausea, abdominal discomfort, and fever with three days of evolution. He was treated with two courses of antibiotic therapy with flucloxacillin to erysipelas previously (3 months and 2 weeks before admission). Lab tests showed serum AST levels of 349 U/L, ALT 646 U/L, alkaline phosphatase 302 U/L, GGT 652 U/L, total bilirubin 3.3 mg/dL and direct bilirubin 2.72 mg/dL. Infectious, autoimmune, and metabolic causes were ruled out. Magnetic resonance cholangiopancreatography showed normal results. Liver biopsy showed mild multifocal (predominantly microvesicular) steatosis; marked changes in the centrilobular areas (sinusoidal dilatation, marked congestion, hemorrhage, and multifocal hepatocyte collapse); expansion of the portal areas with the formation of bridges; proliferated bile ducts and inflammatory infiltrate of variable density, predominantly mononuclear type. The HLA-B*5701 screening test was positive. Hepatic biochemical tests remain abnormal with a significative increase in total bilirubin, which reached levels of 24.1 mg/dL, with the development of jaundice, pruritus, and choluria. DILI was assumed, and the patient was treated with ursodeoxycholic acid. There was favorable evolution, without evidence of blood coagulation dysfunction or encephalopathy. The analytic normalization was, however, slow, with evolution to chronicity. The authors present this case to remind the possibility of moderate/severe drug-induced liver injury to flucloxacillin, an antibiotic commonly used in clinical practice and association with the HLA-B * 5701 allele reported in the literature.

RESUMO A hepatotoxicidade à flucloxacilina é rara e classifica-se como idiossincrática, uma vez que é dependente da suscetibilidade individual, não expectável e independente da dose. Apresentamos o caso de um homem, 74 anos, antecedentes de gamapatia monoclonal e hábitos alcoólicos de 24 g/dia, com quadro de astenia, anorexia, náuseas, desconforto abdominal e febrícula com três dias de evolução. Referência a dois ciclos de antibioterapia com flucloxacilina por erisipela (três meses e duas semanas antes da admissão). Analiticamente com AST 349 U/L, ALT 646 U/L, FA 302 U/L, GGT 652 U/L, bilirrubina total 3,3 mg/dL, bilirrubina direta 2,72 mg/dL. Excluídas etiologias infecciosa, autoimune, metabólica, bem como patologia das vias biliares por colangio-RM. Biópsia hepática mostrou esteatose multifocal ligeira (predominantemente microvesicular); alterações acentuadas nas áreas centrolobulares (dilatação sinusoidal, congestão acentuada, hemorragia e colapso multifocal de hepatócitos); expansão das áreas portais com constituição de pontes; ductos biliares proliferados e infiltrado inflamatório de densidade variável, predominantemente de tipo mononucleado. Tipagem de HLA-B*5701 positiva. Agravamento analítico atingindo bilirrubina total 24,1 mg/dL, com desenvolvimento de icterícia, prurido e colúria. Admitida a hepatotoxicidade, iniciou terapêutica com ácido ursodesoxicólico. Verificou-se evolução favorável, sem evidência de coagulopatia ou encefalopatia. A normalização analítica foi, no entanto, lenta, com evolução para cronicidade. Os autores apresentam este caso para alertar para a possibilidade de hepatotoxicidade moderada a grave à flucloxacilina, antibiótico de uso comum na prática clínica e associação com o alelo HLA-B*5701 relatada na literatura.

The clinical significance of serum autoantibodies and HLA-B27 molecule testing in Uygur patients with human immunodeficiency virus infection / 中华内科杂志

Objective@#To explore the clinical value of serum autoantibodies and human leukocyte antigen (HLA-B27) molecular testing in Uygur patients with human immunodeficiency virus (HIV) infection.@*Method@#A total of 727 HIV-infected Uygur patients who visited Kuche infectious diseases hospital during May 2016 to March 2017 were include in this study. The other 390 healthy people were enrolled as controls. Serum antinuclear antibodies (ANA), anti-cyclic citrullinated peptide (CCP) antibody, anti-extractable nuclear antigen (ENAs) antibody and HLA-B27 molecule were tested.@*Result@#Among 727 HIV-infected Uygur patients, 317 were males and 410 were females with mean age (35.52±13.44) years old. The mean duration of disease was (6.34±3.05) years. There were 697 (95.87%) patients receiving highly active antiretroviral therapy (HAART) with mean duration of treatment (5.52±3.47) years. The mean CD4+T cell count was (520±271) cells/μl in 202 HIV-infected patients, and mean virus load was (108 139±20 498) copies/ml in 20 HIV-infected patients. Rheumatic manifestations were recorded in 238 (32.74%) HIV-infected Uygur patients, mainly with dry mouth and dry eye (15.41%) , alopecia (9.90%) , arthralgia (8.94%) , ect. Compared with the health controls, positive ANA was more common in HIV infected Uygur patients (33.43% vs. 17.43%, P<0.001) with low titers (ANA titer:1∶100) . HIV-infected Uygur patients had higher positive anti-u1-RNP antibodies positive rate (1.10%), but lower anti-SSA antibodies positive rate (0.14%) and anti-CCP antibodies positive rate (0.28%). Patients with positive ANA in HAART group were significantly less than that in non-treatment group (32.71% vs. 50.00%, P=0.049). There were no correlations between ANA and duration of HAART, CD4+T cell counts and virus load (r values 0.061, 0.047, 0.121, respectively. P>0.05). Only one female patient was HLA-B27 positive (0.14%), which was significantly lower than that in healthy controls (3.08%) (P<0.001). Also, only one patient was diagnosed with rheumatoid arthritis (RA).@*Conclusion@#Autoimmune manifestations are common in HIV-infected Uygur patients. Several autoantibodies are positive, but the coincidence of rheumatic diseases is rare. It′s noted that patients with autoimmune manifestations should be considered as a differential diagnosis of HIV infection.

Optimization of HLA-B*27 ALLELE Genotyping by PCR-SSP

OBJECTIVES: HLA-B27 is strongly associated with ankylosing spondylitis (AS) and its presence helps to confirm AS diagnosis. Due to the high HLA polymorphism and the differentiated contribution of alleles and molecules encoded by them, HLA-B*27 allele identification is relevant in the clinical follow-up, diagnosis, and treatment of this spondyloarthropathy. Inexpensive genotyping techniques with high specificity and sensitivity are of great interest in histocompatibility laboratories. This work aimed to optimize HLA-B*27 genotyping by Polymerase Chain Reaction Sequence-specific Primer (PCR-SSP), which is an accessible and inexpensive technique. METHODS: The PCR-SSP was standardized using 26 HLA-B*27 positive and 3 HLA-B*27 negative samples previously defined by Polymerase Chain Reaction Sequence-specific Oligonucleotide Probes (PCR-SSOP) (medium resolution, One Lambda®) and primers described by Duangchanchot et al. (2009). For validating the technique, 397 samples were genotyped using PCR-SSP as well as PCR-SSOP. RESULTS: The PCR-SSP technique was standardized for identifying the alleles HLA-B*27:02, HLA-B*27:CAFRW (05/13/16/17/28/37/38/39/42), HLA-B*27:CAFRZ (08/26/40), HLA-B*27:09 and HLA-B*27:12, which were found in 90 positive samples (22.67%). There was 100% agreement between the two techniques for heterozygous samples; however, two homozygous samples could not be detected by PCR-SSP. CONCLUSION: The HLA-B*27 genotyping using PCR-SSP, an easy-to-use, specific, and affordable technique, was optimized for heterozygous samples. This technique may contribute to AS diagnosis.

A Cross Sectional Study of Sero-prevalence of HLA-B27 among Spondyloarthritis Patients Attending SMS Hospital, Jaipur, Rajasthan

Introduction: Spondyloarthropathies are a heterogeneousgroup of inflammatory interrelated diseases involvingperipheral joints and spine. All forms of spondyloarthropathiesare known to have a strong association with HLA-B27 gene invarious studies done. There was a paucity of literature aboutclinical and demographic characteristics of the HLA-B27positive arthritis patients in Rajasthan. So this study wasplanned to know the seropositivity of HLA-B27 amongseronegative spondyloarthritis patients and to find outassociation between socio-demographic and clinicalcharacteristics and HLA-B27 seroprevalence.Materials and Methods: A cross sectional observational studywas carried out from May 2017 to April 2018 in Department ofPathology, SMS Medical College, Jaipur (Rajasthan). A total of100 cases of spondyloarthritis disease were enrolled in thestudy to find out seroprevalence of HLA-B27 and todifferentiate the clinical and demographic characteristics inHLA-B27 positive and negative patients.Results: In the present study 29% seroprevalence of HLA-B27was observed. Seropositivity of HLA-B27 was significantlyassociated with age (P-value < 0.05) while sex, religion, caste,family history, raised ESR, Positive C-reactive protein, RAfactor etc. were showed no significant association (P-value >0.05).Conclusion: This study confirms the previously reportedassociation in ankylosing spondylitis patients between HLAB27 and earlier disease onset with male preponderance &family aggregation.

HLA-B*44 allele associated with clinical parameters in HIV-1 infected Moroccan cohort

Background: The human leukocyte antigen-B*44 (HLA-B*44) allele has been reported to have promising results in the control of human immunodeficiency virus-1 (HIV-1) infection and associated with protection against HIV-1 disease progression. In the Moroccan HIV-1 infected patients, the contribution of this allele has not been established. This study aimed to evaluate the distribution of HLA-B*44 allele among HIV-1-infected in Morocco. Additionally, investigate HLA-B*44 allele association with demographical and HIV clinical parameters.Methods: One hundred and sixty-seven HIV-1 infected, antiretroviral naive individuals were enrolled in this study. The HLA-B*44 allele screening was performed using the PCR amplification.Results: Of the 167 individuals genotyped, 26 (16%) of them expressing the HLA-B*44 allele. Clinical stages at diagnosis, median pre-treatment HIV viral load (pVL) and CD4 T cell counts differ significantly (p = 0.0001, p=0.001 and p=0.0001 respectively) between the patients who had been expressing the HLA-B*44 allele and patients who had not been expressing this allele. The presence of HLA-B*44 allele was significantly associated with pVL and CD4 T cell counts (p=0.004 and p=0.0001 respectively). The bivariate analysis has showed that the expression of the HLA-B*44 allele was strongly associated with advanced HIV infection (Odd ratio (OR) 0.12 (95% confidence interval (CI) 0.04-0.37), p=0.0001).Conclusions: Author have described for the first time in Morocco the association of the HLA-B*44 allele with the clinical parameters of HIV infection. These results expand the knowledge of the distribution and effect of this allele in the Moroccan population.

Spectrum Of Imaging Appearances On Computed Tomography And Magnetic Resonance Imaging In Ankylosing Spondylitis In Hla B27 Positive Patients In Kumaon Region

AIM: To study the spectrum of imaging appearances on CTand MRI in ankylosing spondylitis with HLAB27 positive patients in kumaon region. Materials and Methods: This was a prospective study conducted in the department of Radiodiagnosis Government Medical College and Dr Susheela Tiwari Memorial Hospital,Haldwani. This study was carried out on 51 cases of ankylosing spondylitis HLAB27 positive cases. C.T. and MRI features were observed on T1weighted, T2weighted and short tau inversion recovery (STIR) sequences. The Spectrum of imaging was studied on the basis of history, clinical evaluation and characteristic radiological features on C.T. and M.R.I. Results: The disease was most commonly seen in adults with a male predominance in 37 (72.5%) cases. Backache (82.4%) was most common clinical feature followed by inflammation in (80%) cases. Lumbar spine was the most common site in 45 (88%) cases with bilaterally symmetrical involvement in 45 (88%) cases. Subchondral sclerosis was better appreciated in C.T. in 34 (66.6%) cases followed by joint erosion in 23 (45%) cases and joint space alteration in 15(29.4%) cases. Whereas, bone marrow oedema 37 (72.5%) cases was better appreciated in M.R.I followed by articular margin irregularity in 34(66.6%) cases and presence of erosion in 32 (62.7%) cases. Conclusion: Imaging is an integral part in the early detection of disease and optimizing management of affected patients for their better prognosis. CTand MRI plays a decisive role in the diagnosis and these modalities are also helpful in monitoring the disease

HLA-B*14 allele predicts HIV-1 mother-to-child-transmission, in Salvador, Brazil

ABSTRACT Background: Class I human leukocyte antigens, especially the molecules encoded at the B locus (HLA-B), are associated with AIDS progression risk. Different groups of HLA-B alleles have been associated to a protective effect or increasing susceptibility to HIV infection and are expressed from the earliest stages of gestation. Objective: The aim of this study was to evaluate which variants of HLA-B are associated with the risk of HIV vertical transmission in infected pregnant women and in their offspring, in a referral center in Salvador Bahia. Methods: We performed HLA-B genotyping in 52 HIV-infected mothers and their children exposed to HIV-1 during pregnancy (N = 65) in Salvador, Brazil. We compared the HLA-B alleles frequency in mothers, uninfected and infected children, according to the use of antiretroviral prophylaxis. Results: Absence of antiretroviral antenatal and postnatal prophylaxis was significantly associated with vertical transmission of HIV-1 (p = <0.01, and p = <0.01 respectively). Frequency of HLA-B*14 (29.2%, p = 0.002), HLA-B*18 (16.7%, p = 0.04) or HLA-B*14:1 (20.8%, p = 0.01) alleles subgroups were significantly higher in HIV-1 infected children and persisted (HLA-B*14, p = 0.04) even after adjusting for use of antiretroviral prophylaxis. No significant difference in expression of HLA-B alleles was observed among mothers who transmitted the virus compared to those who did not. Conclusions: Expression of HLA-B*14 allele in children exposed to HIV-1 is predictive of vertical transmission and reinforces the important role of genetics in mother-to-child transmission.