Referrals for rheumatologic evaluation following a positive antinuclear antibody test result. A cross-sectional single center Brazilian study.

BACKGROUND: In general, patients are referred for rheumatological evaluation due to isolated laboratory abnormalities, especially antinuclear antibody (ANA) positivity, with the risk of more severe patients remaining on the waiting list for longer than desired. The aim of this study was to analyze the demographic, clinical, and laboratory information of patients referred to a specialized rheumatological care unit because of positive antinuclear antibody. METHODS: This is a retrospective study of 99 out of 1670 patients seen by the same rheumatologist between 01/01/2011 and 01/01/2019. Patients whose referrals were exclusively due to the ANA test result and the specialist's final diagnosis being "abnormal finding of serum immunological test" (ICD-10 R769) were included. Sociodemographic, clinical, and laboratory information were extracted from the consulting rheumatologist's chart. Descriptive statistics were used for data analysis. RESULTS: A total of 99 patients were included, most of whom were female (84.8%) with a median age of 49 years. At the moment of specialist's appointment, 97 patients (97.9%) repeated the ANA test, and 77 patients remained positive. Of these, only 35 (35.35%) were in a high titer range (greater than or equal to 1:320). Complete blood count for cytopenia's investigation was not performed in a high percentage of patients (22.2%), as well as urinalysis (31.3%). In addition, more than 70% of patients score 0 to 1 classification criteria for Systemic Lupus Erythematosus, according to SLE - ACR 1987 (American College of Rheumatology) and SLICC 2012 (Systemic Lupus International Collaborating Clinics). CONCLUSIONS: Most patients are still referred for specialized evaluation due to the misinterpretation of laboratory tests that were inappropriately requested in patients without clinical evidence of autoimmune rheumatic disease.

Impact of baseline fluorescent antinuclear antibody positivity on the clinical outcome of patients with primary autoimmune hemolytic anemia.

INTRODUCTION: Autoimmune haemolytic anaemia (AIHA) is an autoimmune disorder that can present in primary or secondary forms. The literature looking at impact of baseline fluorescent antinuclear antibody (FANA) positivity on outcomes of AIHA patients is infrequent. OBJECTIVE: To study the impact of baseline FANA positivity in patients with primary AIHA. METHOD: A prospective cohort study involving 29 consecutive primary AIHA patients presenting to the Haematology department from 2013 to 2015 was analysed. After recording baseline investigations including fluorescent ANA, all patients were treated as per the standard therapeutic protocols. Clinical remission, disease free survival, relapse, mortality were compared between the FANA positive and FANA Negative AIHA groups. RESULTS: Baseline FANA positivity was found in 17 patients (58.62%). Both the groups were comparable in terms of age, sex, Hemoglobin, LDH at presentation, number of lines of treatment needed and duration of follow up. Evan's syndrome was seen in six of FANA positive patients which was statistically significant (0 v/s 6, p = 0.023). FANA positive patients had significantly higher rates of relapse per patient month follow up (1.22 v/s 3.57, p = 0.023) and lower rates of complete response (83.33% v/s 35.29%, p = 0.0118) and relapse free survival at five years. Morbidity and mortality were numerically higher in FANA positive patients. CONCLUSION: Baseline FANA positivity among AIHA patients was found to be associated with lower complete response rates and higher relapse rates with possible higher rates of morbidity. Presence of FANA will give us prognostic value and help us in deciding the treatment options.

Impact of baseline fluorescent antinuclear antibody positivity on the clinical outcome of patients with primary autoimmune hemolytic anemia

Abstract Introduction Autoimmune haemolytic anaemia (AIHA) is an autoimmune disorder that can present in primary or secondary forms. The literature looking at impact of baseline fluorescent antinuclear antibody (FANA) positivity on outcomes of AIHA patients is infrequent. Objective To study the impact of baseline FANA positivity in patients with primary AIHA. Method A prospective cohort study involving 29 consecutive primary AIHA patients presenting to the Haematology department from 2013 to 2015 was analysed. After recording baseline investigations including fluorescent ANA, all patients were treated as per the standard therapeutic protocols. Clinical remission, disease free survival, relapse, mortality were compared between the FANA positive and FANA Negative AIHA groups. Results Baseline FANA positivity was found in 17 patients (58.62%). Both the groups were comparable in terms of age, sex, Hemoglobin, LDH at presentation, number of lines of treatment needed and duration of follow up. Evan's syndrome was seen in six of FANA positive patients which was statistically significant (0 v/s 6, p= 0.023). FANA positive patients had significantly higher rates of relapse per patient month follow up (1.22 v/s 3.57, p= 0.023) and lower rates of complete response (83.33% v/s 35.29%, p= 0.0118) and relapse free survival at five years. Morbidity and mortality were numerically higher in FANA positive patients. Conclusion Baseline FANA positivity among AIHA patients was found to be associated with lower complete response rates and higher relapse rates with possible higher rates of morbidity. Presence of FANA will give us prognostic value and help us in deciding the treatment options.

Antinuclear antibodies in patients with endometriosis: A cross-sectional study in 94 patients.

Markers of autoimmunity, such as autoantibodies, have been found in patients with endometriosis. These include the antinuclear antibodies (ANA). We aimed to evaluate the prevalence of ANA in a sample of patients with endometriosis and its possible clinical associations. Ninety-four patients with endometriosis and 91 controls were studied for ANA and extractable nuclear antigen (ENA; anti-Ro, anti-La, anti-Sm, and anti-RNP) profiles and anti-dsDNA. Epidemiological, clinical, and staging data in endometriosis were obtained. Patients with autoimmune disorders were excluded. Patients with endometriosis had a 21.2% prevalence of positive ANA vs. 5.4% in controls (P = 0.001). The ENA profile and anti-dsDNA were negative. Patients with positive ANA were more asymptomatic (P = 0.03) and had less dysmenorrhea. No associations with disease duration, patient age, or endometriosis stage were found. We found a high prevalence of positive ANA in patients with endometriosis. The presence of this autoantibody may be linked to a milder clinical expression of the disease.

Changes in the result of antinuclear antibody immunofluorescence assay on HEp-2 cells reflect disease activity status in systemic lupus erythematosus.

Background The objective of the study was to determine whether the staining pattern and titer of indirect immunofluorescence assay on HEp-2 cells (HEp-2 IFA) are associated with systemic lupus erythematosus (SLE) disease activity. Methods A total of 269 consecutive patients meeting the ACR and SLICC criteria for SLE were classified into three groups according to the SLE Disease Activity Index 2000 (SLEDAI2K): Remission (SLEDAI2K = 0; n = 47); Intermediate (SLEDAI2K = 1-5; n = 111); Active (SLEDAI2K ≥ 6; n = 111). All subjects were assessed for HEp-2 IFA titer and staining pattern and nine traditional parameters of SLE disease activity. After a 6 to 12-month interval, 101 of the 269 patients were reassessed. Results HEp-2 IFA homogeneous nuclear pattern (AC-1) occurred more frequently in the Active Group compared to the Remission Group (p < 0.001). Fine speckled nuclear pattern (AC-4) tended to occur more frequently in the Remission Group compared to the Active Group (p = 0.054). Subjects with AC-1 pattern had higher SLEDAI (8.8 ± 7.6) than those with AC-4 (4.8 ± 5.2) (p < 0.001). HEp-2 IFA titer and anti-nuclear antibody by enzyme-linked immunosorbent assay (ANA-ELISA) values were lower in the Remission Group compared to the other two groups (p < 0.001). Multivariate analyses identified only ELISA anti-dsDNA as an independent variable associated with disease activity. In follow-up analysis, HEp-2 IFA titer decreased significantly in the 33 subjects with decreased disease activity (p = 0.002). Receiver operator characteristic (ROC) curve analysis for determination of disease activity showed equivalent areas under the curve (AUC) for HEp-2 IFA titer and traditional disease activity parameters. Conclusions HEp-2 IFA pattern and titer can reflect SLE disease activity and may be considered in conjunction with other laboratory and clinical parameters in the assessment of SLE disease activity.

Alopecia areata y vitamina D sérica en pacientes iraquíes: un estudio de casos y controles / Alopecia Areata And Serum Vitamin D in Iraqi Patients: a case-control study

Background: Alopecia areata (AA) is a typical hair issue, which may have obliterating mental and social outcomes and is portrayed by the nearness of nonscarring alopecia. Objective: This examination has targets to assess the serum nutrient D levels , with AA; contrast the outcome and clearly sound control; and confirm relationship between AA types and serum nutrient D levels. Patients Also Methods: the examine might have been led clinched alongside Tikrit educating healing facility throughout those time starting with June 2019 of the limit for January 2020. Irrefutably the quantity of subjects associated with the assessment was ninety individuals isolated in two social events; the patients bundle were forty five the people who whimper of AA while the resulting gathering including a forty five age and sex-made solid volunteers were picked as a benchmark gathering. The degree and movement of the alopecia were noted and the patients were meticulously broke down for signs of various ailments. Research center assessments were led to patients and also to those control population, these included serum vitamin D levels were measured as 25-hydroxyvitamin D {25(OH)D} using a chemiluminescence microparticle immunoassay. Blood models were gotten starting with patients and control subjects after totally taught consent was gotten. Results : An essential complexity may have been found for serum 25-OH Vit D levels between patients other than controls. Vitamin D sufficiency were more common in controls than in patients. Serum Vitamin D was deficient in both cases and controls group; but, the deficiency was significantly more throughout AA group (35. 6%) compared to the handle group (11. 1%). Among the list patients gathering, levels associated with nutrient D were totally higher in guys in contrast with females. Conclusions: AA might be related with nutrient D deficiency as mean degrees of nutrient D of patients were seen as fundamentally lower than typical sound controls.

Antinuclear antibodies and recurrent miscarriage: Systematic review and meta-analysis.

Studies have investigated the relationship between antinuclear antibodies (ANA) and recurrent miscarriage (RM). The objective of this paper is to evaluate the presence of ANA as a risk factor for spontaneous abortion in patients with RM. By considering the guidelines of Preferred Reporting Items for Systematic Reviews and Meta-Analysis, the authors performed systematic review and meta-analysis by searching the databases of PubMed/Medline and SCOPUS. Review Manager, Version 5.3 performed the statistical analysis. Binary variables were analyzed by odds ratio (ORs) and 95% confidence interval (CI). The subgroup analysis compared the effect of different ANA titers. The authors analyzed the ANA patterns of immunofluorescence staining. Seven case-control studies were selected. The frequency of positive ANA was statistically higher in the RM group (20.6%, 288/1400) as compared to the control group (6.7%, 72/1080). The meta-analysis of the positive ANA showed a statistical difference between the two groups (OR 3.30, 95% CI 1.41-7.73; I2  = 87%, P = .006). Studies have revealed different frequencies of ANA patterns of immunofluorescence. This meta-analysis suggested that positive ANA might increase the risk of RM. However, it was not possible to conclude which ANA pattern of immunofluorescence staining is more frequent in the RM group.

Detection of Autoantibodies by Indirect Immunofluorescence Cytochemistry on Hep-2 Cells.

Indirect immunofluorescence assay (IFA) has been used for detection of autoantibodies against cellular antigens for more than 50 years. Originally using rodent tissue as substrate, the method was optimized by using the human immortal HEp-2 cell line derived from a larynx epidermal carcinoma. The HEp-2/IFA platform allows for optimal visualization of several cellular domains recognized by autoantibodies in the samples being tested. Serial dilution allows for the estimation of the concentration (titer) of the autoantibodies in the sample. Judicious analysis of the topographic distribution of the immunofluorescence (pattern) provides useful hints on the most plausible autoantigens being recognized, vis-à-vis the cognate autoantibodies. The importance of the HEp-2/IFA pattern has been recently emphasized by the International Consensus on ANA Patterns (ICAP), an initiative that established a comprehensive classification of the most relevant and prevalent HEp-2/IFA patterns (designated anti-cell (AC) patterns) and harmonized its nomenclature. The former designation "antinuclear antibody test" has been progressively replaced by the term "anti-cell antibody test," due to the recognition that the HEp-2/IFA method in fact allows the detection of autoantibodies to several cellular domains, such as the cytoplasm and mitotic apparatus.The performance of the HEp-2/IFA test is strongly influenced by several technical details, including cell culture conditions, cell fixation and permeabilization methods, choice and titration of fluorochrome-conjugated secondary antibody, use and choice of blocking solutions, washing buffers, and antifading mounting medium. The several steps of the procedure must be carefully performed in order to avoid the formation of false positive fluorescent artifacts. The quality control of the assay involves the use of serum standards for negative, low positive and strongly positive reaction in each run of the assay. In addition, every new lot or new brand of HEp-2 slides should be evaluated by using a panel of standard sera yielding the most relevant AC patterns. Special attention should be dedicated to the training of personnel for the analysis of the slides at the microscope. These should be able to identify possible artifacts, recognize all relevant AC patterns, and formulate possible reflex tests according to the observed AC patterns.

Systemic lupus erythematosus onset in lupus-prone B6.MRL/lpr mice Is influenced by weight gain and Is preceded by an increase in neutrophil oxidative burst activity.

In this study, we assessed whether weight gain influenced the systemic lupus erythematosus (SLE) onset and/or outcome, and examined the role that reactive oxygen species (ROS) production by neutrophils played in the SLE onset and/or outcome. Female control (C57BL/6) and lupus-prone B6.MRL/lpr mice (CM and LPM, respectively) at 4 weeks old were fed standard diet or standard diet plus cafeteria diet during 12 weeks. SLE diagnosis relied on the presence of both antinuclear antibodies (ANA) and renal abnormalities. We found that the percentage of weight gain in CM and LPM increased as a function of the length of cafeteria diet feeding period, but it was not associated with energy intake. Cafeteria diet-fed CM and LPM at 8 and 12 weeks old were overweight, while CM and LPM at 16 weeks old were obese. Compared with standard diet-fed CM and LPM, cafeteria diet-fed CM and LPM exhibited elevated glucose and total cholesterol levels, and diminished triglycerides levels. Standard diet-fed 16-week-old LPM and cafeteria diet-fed 12-week-old LPM had nephritis, characterized by the increased interstitial infiltration of leukocytes. Cafeteria diet-induced weight gain rose the frequency of homogeneous and speckled ANA staining patterns in the 12- and 16-week-old LPM groups. Together, these results indicated that weight gain anticipated the SLE onset. In addition, neutrophils from cafeteria diet-fed 8-week-old LPM exhibited augmented ROS production capacity; in standard diet-fed LPM, such rise occurred only in the 16-week-old group. Thus, the neutrophil ROS production capacity was increased before the SLE onset and during its outcome. Overweight and obese CM and LPM displayed elevated levels of kidney, liver, heart, and spleen lipid peroxidation. In conclusion, cafeteria diet-induced weight gain is associated with the increased production of ANA and neutrophil-derived ROS, which may contribute to accelerate the SLE onset.

[Seroprevalence of antinuclear antibodies in blood donors in the Yaqui Valley]. / Seroprevalencia de anticuerpos antinucleares en donadores de sangre del valle del Yaqui.

BACKGROUND: Antinuclear antibodies are immunoglobulins that recognize autologous nuclear and cytoplasmic cellular components. In healthy persons they are not associated with autoimmune disease. However, they may be related to an immune risk phenotype that has not been sufficiently studied. We undertook this study to examine the presence of antinuclear antibodies in serum from blood donors. METHODS: Cross-sectional study on 379 blood donors between 18 and 65 years old. Serum for the presence of antinuclear antibodies by indirect immunofluorescence in HEp-2 cells was analyzed. The prevalence and pattern of expression were compared with age, gender, and history of rheumatic or thyroid disease. RESULTS: Prevalence of antinuclear antibodies in the study population was 13%. Most of the positive subjects were between 21 and 40 years old. Male gender expressed a greater proportion of positivity (11%) than females (2%). Likewise, 82% of males had low titers (1:80) and nucleolar type in 66% of cases (OR = 10.66 [1.83 to 62.18], p = 0.007). CONCLUSIONS: The presence of antinuclear antibodies in healthy individuals at low levels may not mean an autoimmune condition; however, it could reflect exposure to environmental factors that have not been sufficiently studied. New studies of healthy individuals are necessary in order to explain the association between the presence of these antibodies and toxic and environmental factors and their effects on health.

Antecedentes: los anticuerpos antinucleares son inmunoglobulinas que reconocen componentes celulares nucleares y citoplasmáticos autólogos. En personas sanas no se relacionan con alguna enfermedad autoinmune; sin embargo, pueden estar vinculados con un fenotipo inmunológico de riesgo que no ha sido suficientemente estudiado. Objetivo: examinar la existencia de anticuerpos antinucleares en el suero de donadores de sangre. Material y métodos: estudio transversal y analítico en búsqueda de anticuerpos antinucleares en suero mediante inmunofluorescencia indirecta en células HEp-2. La prevalencia y patrón de expresión se contrastaron con la edad, el género y los antecedentes de enfermedad reumática o tiroidea. Resultados: se estudiaron 379 donadores de sangre con límites de edad entre 18 y 65 años. La prevalencia de anticuerpos antinucleares en la población estudiada fue de 13%. La mayoría de los sujetos positivos tenía entre 21 y 40 años de edad. El género masculino expresó mayor proporción de positividad (11%) en comparación con las mujeres (2%). De la misma forma, 82% de los hombres tenía títulos bajos (1:80) y en 66% eran de tipo nucleolar (RM = 10.66 [1.83 a 62.18]; p = 0.007). Conclusiones: en individuos sanos, la existencia de anticuerpos antinucleares a títulos bajos puede no significar un estado de autoinmunidad; sin embargo, podría ser el reflejo de una exposición a factores ambientales que no han sido lo suficientemente estudiados. Es necesario realizar nuevos estudios en población sana que permitan explicar la asociación entre estos anticuerpos y los factores tóxicoambientales, así como sus efectos en la salud.

Glomerulonefrite lúpica em paciente com FAN Negativo / Lupus Glomerulonephritis in Patient with Negative ANA (Antinuclear Antibody)

O lúpus eritematoso sistêmico (LES) é uma doença autoimune, inflamatória e crônica com manifestações sistêmicas. A glomerulonefrite é conhecida como uma das complicações mais comuns do LES. As manifestações renais são difíceis de caracterizar e a nefrite lúpica é um preditor importante do prognóstico. O fator antinuclear (FAN) geralmente é detectado em 95% dos pacientes com LES. Em casos de FAN negativo, a biópsia renal, é necessária porque, além de estabelecer a classificação histológica, tem implicações prognósticas e terapêuticas e exclui outras possibilidades diagnósticas. No presente trabalho é apresentado um caso de uma paciente feminina de 30 anos com glomerulonefrite FAN negativa após uma gravidez complicada por doença hipertensiva associada à gravidez, sendo diagnosticada com LES através de biópsia renal característica.

Systemic lupus erythematosus (SLE) is an autoimmune disease, and inflammatory disorder with systemic characteristics. Glomerulonephritis is known as one of the most common complications of SLE. The renal manifestations are difficult to characterize and lupus nephritis is an important predictor of prognosis. The antinuclear antibodies (ANA) are usually detected in 95% of patients with SLE. In cases of ANA negative, renal biopsy is necessary because, in addition to establishing the histological classification, has prognostic and therapeutic implications and exclude other diagnostic possibilities. In this paper we present a case of a 30 years old female, with an ANA negative glomerulonephritis after a Specific Hypertensive Disease of Pregnancy that was diagnosed as lupus because of a characteristic renal biopsy.

Esclerodermia infantil a propósito de un caso / Infant sclerodermia: case report

Reporte de caso clínico, correspondiente a paciente de tres años de edad, que ingresó al servicio de Pediatría del hospital regional de Portoviejo por presentar fiebre, esclerodactilia, atrofia muscular y lesiones dérmicas que progresaron de una fase eritematosa a una dermis atrófica, tensa e inmóvil. Se realizaron varias pruebas clínicas e inmunológicas, determinándose factor reumatoide y anticuerpos antinucleares. Estudio histopatológico mostró atrofia dérmica con fibrosis. Como medida terapéutica se usó corticosteroides, con lo que mejoró el cuadro clínico. Sobre esta enfermedad, se realiza una descripción resumida.

Case report of a 3 year old patient admitted to the Pediatric Service of Portoviejo regional hospital presenting fever, sclerodactilia, muscular atrophy and dermatologic lesions which progressed form an erytrhematous fase to a tense and montionless atrophic dermis. Many clinical and immunologic tests were taken, determinating rheumatoid factor and antinuclear antibody. Histopatological studies showed atrophy dermis with fibrosis. Using corticosteroids as a therapeutic measure improved the clinical course.