Combination of cytoplasmic and nuclear patterns on Hep-2 antinuclear antibody is useful as a screening test for anti-synthetase syndrome.

OBJECTIVE: This study aimed to establish a screening model for differentiating anti-synthetase syndrome (ASS) from other antinuclear antibody (ANA)-associated rheumatic diseases (AARD) using a combination of cytoplasmic and non-cytoplasmic ANA (ncANA) patterns. METHODS: This retrospective observational study included patients with AARDs such as systemic lupus erythematosus (SLE), systemic sclerosis (SSc), Sjögren's syndrome (SS), mixed connective tissue disease (MCTD), and polymyositis/dermatomyositis (PM/DM) who underwent ANA screening between April 2012 and December 2021. Variables included age, sex, ANA patterns (Cytoplasmic and ncANA), and titers. Logistic regression analysis of Cytoplasmic and ncANA patterns was performed to differentiate ASS from other AARDs. RESULT: The 981 diagnosed cases of AARDs consisted of SS (n = 451), SSc (n = 264), SLE (n = 201), PM/DM (n = 104), MCTD (n = 52), and ASS, including PM/DM (n = 64). Of these, 155 patients had ≥2 overlapping diseases; however, there was no overlap between AARDs and ASS. ASS is more likely to occur when the cytoplasmic titer is positive and the ncANA <320. Receiver operating characteristic (ROC) analysis of the Cytoplasmic and ncANA range revealed an area under the ROC curve (AUC) of 0.885 (95% CI: 0.844 to 0.927). CONCLUSION: It is important to detect cytoplasmic patterns as an ANA screening test for ASS diagnosis, even if the titer is low. Additionally, combining the cytoplasmic and ncANA patterns yields more accurate ASS screening results.

The presence of autoantibodies as a potential prognostic biomarker for breast cancer.

The presence of autoantibodies is closely associated with the occurrence and development of cancer. Autoantibodies can be used as biomarkers for early breast cancer diagnosis. However, the relationship between autoantibodies and the prognosis of breast cancer patients remains elusive. This retrospective study aimed to investigate the correlation between the presence of autoantibodies and outcomes in breast cancer patients. This study included a total of 155 patients from People's Hospital of Henan University (Zhengzhou, China) who were diagnosed with breast cancer from January 2017 to December 2021. The enrolled patients' clinicopathological features were collected, and 88 patients were ultimately involved in the analysis. Univariate and multivariate Cox regression analyses were performed to search for the risk factors related to the poor prognosis of breast cancer patients. The association between the presence of autoantibodies and patients' survival was analysed using Kaplan-Meier curves. After screening, there were 38 autoantibody-positive cases and 50 autoantibody-negative cases. Breast cancer patients with autoantibody-positive had a 57% lower risk of death compared with autoantibody-negative patients. Multivariate Cox regression analysis indicated that the presence of autoantibody could be a potential prognostic predictor for breast cancer, independent of age, histological grade, pathological classification, clinical stage, and the expression levels of hormonal receptors. In addition, autoantibody-positive breast cancer patients had longer progression-free survival and overall survival compared with autoantibody-negative cases. Positive autoantibody was found as an independent biomarker of better prognosis in breast cancer patients, providing a new strategy for the prognostic assessment of breast cancer patients.

Elevated levels of anti-Golgi antibodies: An early sign of seronegative rheumatoid arthritis.

Anti-Golgi antibodies are uncommon antibodies that exhibit specific, polarized cytoplasmic staining on the Hep-2 substrate. The objective of our study was to identify the clinical and laboratory features associated with anti-Golgi antibodies. We examined 4.5 years of data from a Turkish tertiary hospital in this retrospective cohort analysis. The indirect immunofluorescence staining patterns, antinuclear antibody (ANA) titres and clinical data of all patients were obtained from the hospital record system. A total of 146,055 ANAs were detected, of which 224 patients (0.15%) exhibited anti-Golgi antibody staining. In total, 39.4% of diagnosed patients had autoimmune diseases (AIDs). Of the AIDs, 26 (46.4%) were rheumatoid arthritis (RA). This is a very high rate and another remarkable point is that 17 (65.3%) of these patients had seronegative RA. High-titre results (1 ≥ 1/320) were more common in patients with AID. Anti-Ro52 was prevalent in 50% of extractable nuclear antigen (ENA)-positive patients, making it a remarkable finding. The majority of individuals with high-titre anti-Golgi antibodies had AID, particularly RA. The majority of these patients also tested negative for anti-cyclic citrullinated peptide (anti-CCP) and rheumatoid factor (RF). Finally, high-titre anti-Golgi antibodies may be an important serologic marker for seronegative RA in the Turkish population.

Anticentromere antibodies are the most potent antinuclear antibodies in reducing live birth outcomes after ICSI.

RESEARCH QUESTION: How, and to what extent, do anticentromere antibodies (ACA) reduce live birth outcomes after ICSI? STUDY DESIGN: Retrospective cohort study of infertile women aged 30-43 years who underwent ICSI between September 2016 and March 2021. Women with a history or current diagnosis of symptomatic connective tissue disease were excluded. Immunofluorescence staining detected antinuclear antibodies (ANA). Staining pattern and titre (cut-off, 1:160) were used to divide infertile women into three groups: positive for ACA (ACA+) (n = 28); positive for ANA other than ACA (ANA+) (n = 77); and negative for both ACA and ANA (control) (n = 3723). RESULTS: Cumulative live birth rate (CLB) was lowest in ACA+ (7%, 31% and 46% in ACA+, ANA+ and control, respectively) (ACA+ versus control, P < 0.0001; ACA+ versus ANA+, P = 0.011; ANA+ versus control, P = 0.012). A small impairment in meiosis I and a larger impairment in meiosis II, fertilization and embryo cleavage caused the decrease. Multiple pronuclei formation increased (RR versus control, 5.33; 95% CI 4.26 to 6.65) and good-quality blastocyst development decreased (RR 0.34; 95% CI 0.22 to 0.53). Multiple logistic regression analysis showed that ACA was associated with CLB outcome (OR 0.08, 95% CI 0.02 to 0.36); the other four ANA staining patterns were not. CONCLUSIONS: The effect of ACA on live birth outcomes is strongest after ICSI among ANA, primarily through the impairment of meiosis II and subsequent stages. Repeated ICSI failure and eggs with multiple pronuclei may warrant specific testing for ACA.

Clinical significance of antinuclear antibody as prognostic marker for first-line pembrolizumab in advanced non-small cell lung cancer.

BACKGROUND: The relationship between antinuclear antibody (ANA) and the efficacy of programmed death-1 (PD-1) blockade remains controversial. Here, we investigated the prognostic significance of ANA titer in patients with non-small cell lung cancer (NSCLC) receiving pembrolizumab monotherapy as the first-line treatment, compared with that of platinum-based chemotherapy with PD-1 blockade. METHODS: Our clinical data based on the ANA titer (1:80) were retrospectively reviewed for patients with advanced NSCLC, who were treated with first-line pembrolizumab monotherapy and platinum-based chemotherapy with PD-1 blockade. Immunohistochemical staining for tumor-infiltrating lymphocytes such as CD4, CD8 and Foxp3 was performed. RESULTS: Among 106 patients treated with pembrolizumab, 19 (17.9%) tested high for ANA. Progression-free survival (PFS) and overall survival (OS) were significantly better in patients with high ANA than in those with low ANA, and high ANA was identified as an independent prognostic predictor, particularly in the subgroup with programmed death ligand-1 (PD-L1) ≥ 50%. However, no statistically significant difference in PFS and OS based on the ANA titer was observed in 59 patients treated with combinational chemotherapy and immunotherapy. High numbers of intratumoral Foxp3 and stromal CD8 were significantly associated with low ANA. CONCLUSIONS: Assessment of preexisting ANA titers was useful to prognose PD-1 blockade as a first-line setting, particularly for the PD-L1 ≥ 50% subgroup, but not in the case of combined immunotherapy and chemotherapy.

Autoimmunity and epithelial dysplasia in patients with oral lichenoid diseases.

OBJECTIVES: The primary objective of this study was to explore relationship between autoimmunity and epithelial dysplasia in patients with oral lichenoid diseases. MATERIALS AND METHODS: A total of 66 patients with oral lichen planus (OLP), 35 with oral lichenoid lesion (OLL), and 85 with oral lichenoid drug reaction (OLDR) were enrolled. OLP, OLL, and OLDR were diagnosed following the definitions of the modified World Health Organization criteria, except for the absence of epithelial dysplasia. All patients underwent diagnostic incisional biopsy and adjunctive direct immunofluorescence assays. An indirect immunofluorescence assay was conducted to determine the antinuclear antibody (ANA) positivity. RESULTS: OLP and OLDR patients with epithelial dysplasia demonstrated higher prevalence of serum ANA positivity compared to those without epithelial dysplasia. Elevated serum levels of high sensitivity-C reactive proteins were observed in the OLP, OLL, and OLDR patients with epithelial dysplasia. In the DIF analysis, patients with epithelial dysplasia in the OLP exhibited a higher prevalence of C3 deposition in the basement membrane zone. CONCLUSIONS: This study proposed that autoimmunity may contribute to elevating levels of focal and chronic systemic inflammation, potentially influencing abnormal wound healing and development of dysplastic changes in the oral epithelium among patients with oral lichenoid disease.

The effect of antinuclear antibody titre and its variation on outcomes in children with primary immune thrombocytopenia.

Antinuclear antibody (ANA) can be positive in children with primary immune thrombocytopenia (ITP), but the effect of ANA titre and its variation on outcomes of children with primary ITP remains unclear. Here, we conducted a single-centre retrospective cohort study of children with primary ITP at the Peking Union Medical College Hospital in China. A total of 324 children with primary ITP included in this study were followed for a median time of 25 months. In this cohort, 39.2% had an ANA titre of 1:160 or higher. Results from a generalized estimating equation model revealed that patients with higher ANA titres had lower platelet counts at onset but a higher recovery rate of subsequent platelet counts. Results from Cox regression models adjusted for potential confounders revealed that patients with ANA titres of 1:160 or more were more likely to develop to autoimmune disease (AID) than those without, and the risk of AID development increased with the rise of ANA titres (p value for trend less than 0.001). These data highlight the predictive value of ANA titre for platelet counts and the risk of AID development in children with primary ITP.

Antinuclear antibody (ANA) status predicts immune-related adverse events in liver cancer patients undergoing anti-PD-1 therapy.

Immune-related adverse events (irAEs) clinically resemble autoimmune diseases, indicating autoantibodies could be potential biomarkers for the prediction of irAEs. This study aimed to assess the predictive value of peripheral blood antinuclear antibody (ANA) status for irAEs, considering the time and severity of irAEs, as well as treatment outcome in liver cancer patients administered anti-PD-1 therapy. Ninety-three patients with advanced primary liver cancer administered anti-PD-1 treatment were analyzed retrospectively. They were divided into the ANA positive (ANA+, titer ≥ 1:100) and negative (ANA-, titer < 1:100) groups. Development of irAEs, progression-free survival (PFS), and overall survival (OS) were assessed. Compared with ANA- patients, ANA+ cases were more prone to develop irAEs (43.3% vs. 19.2%, P = 0.031). With the increase of ANA titers, the frequency of irAEs increased. The time interval between anti-PD-1 therapy and the onset of irAEs was significantly shorter in ANA+ patients compared with the ANA- group (median, 1.7 months vs. 5.0 months, P = 0.022). Moreover, the time between anti-PD-1 therapy and irAE occurrence decreased with increasing ANA titer. In addition, PFS and OS were decreased in ANA+ patients compared with the ANA- group (median PFS, 2.8 months vs. 4.2 months, P = 0.043; median OS, 21.1 months vs. not reached, P = 0.041). IrAEs occur at higher frequency in ANA+ liver cancer patients undergoing anti-PD-1 therapy. ANA titer could help predict irAE development and treatment outcome in these patients.

Association between antinuclear antibody and female infertility: A meta-analysis.

Autoimmunity is reported involving in reproductive failures, and antinuclear antibody (ANA) positivity has been regarded as a typical feature of autoimmunity. Published studies on the association of ANA with reproductive failures including infertility are controversial. The aim of this meta-analysis was to analyse whether the presence of ANA positivity increases the risk of infertility in women. We searched the PubMed and Embase databases for relevant literature without any restrictions prior to April 28, 2021. All analyses were performed using the RevMan 5.3 software. Twelve studies with 2734 participants, including 1482 patients with infertility, met the inclusion and exclusion criteria. The total positivity rate of ANA was 23.8% (353/1482) in all infertile patients and 8.5% (107/1252) in the control group. Infertile females had a significantly higher ANA positivity rate than the control group (odds ratio [OR] = 2.90, 95% confidence interval [CI]: 1.72-4.87, I2 = 65%, P < .0001). Several subgroup analyses were performed to reduce the heterogeneity. ANA positivity was associated with female infertility in studies either performed by indirect immunofluorescence (OR = 2.26, 95% CI:1.67-3.06, P < .00001) or by ELISA (OR = 10.76, 95% CI:1.82-63.64, P < .00001). ANA was significantly associated with increased risk of women infertility either after the definite exclusion of individuals with autoimmune diseases (AID) or without exclusion [(OR = 1.99, 95% CI:1.29-3.06, P = .002), (OR = 2.76, 95% CI:1.56-4.88, P = .0005), respectively]. This meta-analysis provides a comprehensive overview of the prevalence of antinuclear antibodies (ANA) in infertile women and suggests that ANA positivity increases the risk of infertility.

Iatrogenic ANA: An emerging source of expensive diagnostic confusion.

Intravenous immune globulin (IVIg) therapy has been shown to be useful in a multitude of disorders. IVIg is produced from pooled human plasma; therefore, autoantibodies found in the general population are also present in IVIg and transferred to those being transfused. This can prove a particular hazard for screening and diagnostic tests based on autoantibodies. We present a patient who was found to have a positive antinuclear antibody (ANA) titer after multiple IVIg transfusions, resulting in diagnostic confusion and unnecessary workup. A 45-year-old gentleman was diagnosed with atypical CIDP, initiated on a course of IVIg, and sent for inpatient rehabilitation. However, recovery was complicated by multiple readmissions for recurrent weakness, and as part of the workup for other etiologies, an ANA was found to be positive. Sub-serologies and paraneoplastic autoantibody panel were negative. In the absence of clinical symptoms, we recommended continued monitoring and repeat ANA testing 6 months after the last dose of IVIg; as any drug needs 5 half-lives to be eliminated from the body. Clinicians should consider any recent IVIg treatments when evaluating the pre-test probability of detecting an underlying connective tissue disease with ANA screening. Indiscriminate ANA levels in patients recently given IVIg lead to unnecessary and expensive further testing and consultation.

Anti-topoisomerase 1 Antibody Level Changes after B Cell Depletion Therapy in Systemic Sclerosis.

The aim of our study was to assess the relationship between the changes of antinuclear autoantibodies (ANAs) and autoantibodies to topoisomerase 1 (anti-Topo 1) in systemic sclerosis (SSs) patients on rituximab (RTX) therapy. The prospective study included 88 patients (73 women) with a mean age of 47 (17-71) years. The mean disease duration was 5.9 ± 4.8 years. The mean follow-up period was more than 2 years (27 (12-42) months). We documented a statistically significant change in skin score, the disease activity index, improvement of pulmonary function and reduction of mean dose of prednisolone after RTX treatment. There was a significant decrease in the number of patients with high levels of ANA and overall decrease of the ANA and anti-Topo 1 levels. A moderate positive statistically significant correlation was found between ANA and anti-Topo 1 (r = 0.403). In the group of patients positive for anti-Topo 1 there were a more pronounced depletion of B lymphocytes, significantly higher increase in forced vital capacity and diffusion capacity, decrease in the disease activity index, compared with patients negative for anti-Topo 1. We observed the decline in the level of ANA and anti-Topo 1 in SSc patients after RTX therapy, and it was correlated by an improvement of the main outcome parameters of the disease. Therefore, anti-Topo 1 positivity could be considered as a predictor of a better response to RTX treatment, especially in SSc patients with hyperproduction of anti-Topo 1.

Significance of the immunofluorescence staining patterns and titres of the antinuclear antibody test in paediatric rheumatology setting.

BACKGROUND: Antinuclear antibody (ANA) is among the most frequently ordered tests in paediatric rheumatology setting. Diseases like systemic lupus erythematosus and Sjögren syndrome is closely related with a positive ANA and classified as ANA associated diseases. Besides, ANA test is ordered in patients with juvenile idiopathic arthritis (JIA) to assess the risk for uveitis and a positive ANA could be detected in children with nonrheumaticrheumatic conditions. In this study, we aimed to investigate frequency of positive ANA in paediatric rheumatology setting and the association of immunofluorescence staining patterns and titres of ANA with rheumatic diseases. METHODS: : Immunofluorescence staining patterns, and titres of the ANA and diagnoses of children who tested for ANA between January 2016 and December 2021 were retrospectively analysed. RESULTS: Among 2477 patients with ANA tested, 28.1% had a positive ANA result. Among them, 39.2% had a diagnosis of a rheumatic disease. Most common rheumatic diagnosis was JIA (43.8%) and ANA associated diseases were observed in 24.5% of the patients with a rheumatic diagnosis. While ANA associated diseases had significantly more frequent homogenous staining, dense fine speckled pattern was significantly more common in children with nonrheumatic diagnoses. Despite ANA associated diseases was found to be significantly associated with higher titres, no difference was observed between patients with JIA and nonrheumatic conditions. DISCUSSION: Our study showed that the majority of children with a positive ANA test were not diagnosed with a rheumatic disease. While titres and patterns of ANA were found to be important in diagnosis of rheumatic diseases, ordering ANA test with solid indications might give improved probability of rheumatic diagnoses in children with a positive test.

Relations between antinuclear, antineutrophil cytoplasmic, anticardiolipin antibodies and degree of neurological deficit, cerebrovascular stenosis in cerebral infarction patients.

Objective: To investigate the correlation of antinuclear antibody (ANA), antineutrophil cytoplasmic antibody (ANCA) and anticardiolipin antibody (ACA) with the degree of the neurological defect and cerebrovascular stenosis in patients with cerebral infarction. Methods: Clinical data of 99 patients with acute cerebral infarction (ACI) admitted to the Department of Neurology of Baoding First Central Hospital from June 2020 to December 2021 were retrospectively analyzed, and their ANA, ACA, ANCA, neurological deficit (NIHSS) scores as well as cerebrovascular stenosis were detected and assessed. Moreover, the correlation between the positive expression rates of ANA, ANCA, ACA and the degree of the neurological deficit, as well as the location and degree of cerebrovascular stenosis, were analyzed. Results: All patients had ANA, ACA, ANCA antibodies with positive rates of 68.69%, 70.71%, 69.70%, and mild, moderate, and severe cerebrovascular stenosis with incidence rates of 28.28%, 32.32%, and 39.39% respectively; Moreover, their incidence of mild, moderate, and severe neurological deficits were 15.15%, 44.44%, and 40.40%, respectively. Statistically significant differences could be observed in the degree of cerebrovascular stenosis and neurological deficit between the ANA, ACA and ANCA antibody positive group and the negative group (p<0.05). ANA, ACA, ANCA antibody positive was moderately positively correlated with cerebrovascular stenosis rate and NIHSS score (0.40

Potential risk factors for the development from immune thrombocytopenia to systemic lupus erythematosus: a case-control study in Chinese children.

Immune thrombocytopenia (ITP) patients are at risk developing to systemic lupus erythematosus (SLE) in the future. Our study attempted to explore the potential risk factors for the development from ITP to SLE in Chinese children by statistical analysis. This study was a retrospective case-control study. Patients diagnosed with ITP and developed to SLE after the diagnosis of ITP were defined as the case group. The control group consisted of children with ITP but without developing to SLE was recruited with a ratio of 1:2. Besides univariable analysis, multivariable logistic regression was built to evaluate the potential risk factors. A total of 150 children was included with 50 in the case group and 100 in the control group. Median developing time from ITP to SLE was 34.5 [IQR 12.5, 58.75] months. ANA was found significantly different between the two groups in our study in the univariable analysis but not in the multivariable analysis (OR = 4.50, 95% CI 0.97 to 21.01). Age diagnosed ITP was positively associated with SLE (OR = 1.07 every 5 years, 95% CI 1.01 to 1.15) with alert point at 8 years old (sensitivity 0.82, specificity 0.60). A lower level of complement was also positively associated with SLE (OR = 8.33, 95% CI 1.62 to 42.91). A minimum 3-year of close follow-up for pediatric ITP patients was recommended to monitor the risk for developing SLE. Older age and hypocomplementemia were potential risk factors for the development from ITP to SLE.

[Analysis of clinical features and prognosis of acute severe autoimmune hepatitis].

Objective: To analyze the clinical features and prognosis of acute severe autoimmune hepatitis (AIH). Methods: A retrospective analysis of the clinical data of patients with acute severe AIH admitted to our hospital from 2008 to 2019 was divided into acute AIH (A-AIH) and chronic acute AIH (AC-AIH) according to the presence or absence of liver diseases. Patients' general condition, liver biochemistry, immunology, histological features of liver, hormonal therapies prognosis and related factors were analyzed. Results: A total of 41 cases [39 females, age (54.24 ± 10.55) years] were collected. Alanine aminotransferase (ALT) and total bilirubin (TBil) were significantly increased, and the international normalized ratio (INR) was > 1.5. Acute lobular inflammation was the feature of acute and severe AIH in the histology of liver. The serum IgG level was (28.36 ± 8.35) g / L. The positive rate of antinuclear antibody (ANA) and anti-smooth muscle antibody (ASMA) was 82.9%, and 17.1%, respectively. Over 70% of acute severe AIHs were AC-AIH. The duration of onset of AC-AIH was > 8 weeks, while most A-AIHs < 8 weeks, and the differences between the two groups were statistically significant (P = 0.001). The mortality rate within 30 days after hormonal treatment was 19.5%. There were statistically significant differences in TBil, Model for End-Stage Liver Disease (MELD) score and leukocyte count between the death and survival group. Conclusion: The mortality rate in acute severe AIH is high, and most of them have the basis of chronic liver disease. Serum IgG level, autoantibodies and acute lobular inflammation are important factors for diagnosis. The prognosis of hormonal therapy is related to the patients' condition and course of disease.

Assessment of ideal serum dilution for screening of antinuclear antibodies by an indirect immunofluorescence method in diagnosis of autoimmune disorders.

BACKGROUND: Time and cost constraints lead to majority of clinical laboratories deviating away from an ideal practice of checking for antinuclear antibodies (ANAs) by indirect immunofluorescence (IIF) at multiple dilutions. Usage of screening dilution of 1:40 recommended by most manufacturers of commercial ANA kits results in numerous false positive-tests and misdiagnosis of connective tissue disorders (CTDs). We sought to study the ideal screening dilution for ANA by IIF for a diagnosis of ANA-related CTDs. METHODS: Serum samples of patients with ANA-related conditions (n = 233) and healthy controls (n = 154) were evaluated by IIF using Immuno Concepts Hep-2000 ® ANA kits at dilutions from 1:40 to 1:640. Accuracy for diagnosis of CTDs for each serum dilution was assessed by receiver operating curve (ROC) analysis. RESULTS: Antinuclear antibodies (ANA) positivity was observed in 19.5%, 10.4%, 4.55%, 0.65%, and 0% of healthy controls at dilutions of 1:40, 1:80, 1:160, 1:320, and 1:640, respectively. ANA positivity at 1:40 dilution was observed among 26.4% cases with mimics of CTDs. Prevalence of ANA positivity in ANA-related CTDs was 97.3%, 96.4%, 89.3%, 83.9%, and 71.4% at dilutions of 1:40, 1:80, 1:160, 1:320, and 1:640, respectively. ROC analysis revealed best test performance for distinction between healthy and ANA-related CTD populations at a serum dilution of 1 in 80. CONCLUSIONS: Antinuclear antibodies (ANA) positivity at low titers (1:40) is highly prevalent in healthy population (19.5%) as well as amongst mimics of CTD (26.4%). Our study suggests a higher screening dilution of 1:80 for ANA by IIF for diagnosis of CTD maybe better. Combination of 1:80 and 1:160 dilutions provides optimum sensitivity and specificity for diagnosis of ANA-related disorders.

Clinical characteristics and treatment outcomes of acute severe autoimmune hepatitis.

BACKGROUND AND AIM: Acute severe autoimmune hepatitis (AS-AIH) is a rare cause of acute liver failure (ALF), which is often neglected and delayed in treatment. The purpose of this study was to analyze the clinical characteristics and therapeutic effects of AS-AIH. METHODS: Retrospective analysis was performed. AIH was diagnosed according to the International Autoimmune Hepatitis Group (IAIHG) criteria revised in 1999. AS-AIH was defined as an acute presentation (onset of symptoms to presentation of ≤ 26 weeks) and INR of ≥ 1.5, and no histologic evidence of cirrhosis. RESULTS: Twelve patients were diagnosed as AS-AIH. At baseline, median immunoglobulin G was 28.35 g/L (range, 11.4-49.2). Ten (83.3%) patients were antinuclear antibodies and/or anti-smooth muscle antibodies positive. The prominent histologic characteristics were lobular necrosis/inflammation (91.7%) and plasma cell infiltration (100%). All patients received corticosteroid therapy. Death occurred in 2 (16.7%) patients within 30 days resulted from ALF. The average interval between the onset of symptoms and initiation of corticosteroid therapy in deceased patients was 65 days, compared with 19 days for survivors. CONCLUSIONS: AS-AIH is an uncommon disease with poor outcomes. Patients with acute severe hepatitis of unknown cause should be minded the possibility of AS-AIH and corticosteroids should be considered as soon as possible.

In vitro diagnostics for the medical dermatologist. Part I: Autoimmune tests.

Despite the expansion of available in vitro laboratory tests at a rate far exceeding that of dermatologic pharmaceuticals, the existing literature is dominated by discussion of the latter. With the advent of numerous new tests, it can be difficult for practicing dermatologists to stay up-to-date on the available options, methodologies, and recommendations for when to order one test over another. Understanding the inherent strengths and weaknesses of these options is necessary to inform appropriate ordering and proper interpretation of the results. The first article in this continuing medical education series summarizes information on methodology, test characteristics, and limitations of several in vitro laboratory tests used for the work up of undifferentiated patients suspected of having dermatologic autoimmune diseases and it provides a general guide to ordering these tests.

Immunologic markers, vasculitis-associated autoantibodies, and complement levels in patients with COVID-19.

BACKGROUND: The cause of coronavirus disease 2019 (COVID-19) is a virus which can lead to severe acute respiratory syndrome-CoV-2 (SARS-COV-2). There are evidences of involvement of immune system in pathogenesis of this disease. We investigated the presence of various vasculitis-associated autoantibodies and complement levels in patients with COVID-19. MATERIALS AND METHODS: Patients with severe or critical type of COVID-19 were evaluated for symptoms, signs, and laboratory tests of vasculitis syndromes including rheumatoid factor (RF), antinuclear antibody (ANA), anti-double-stranded DNA, c and p anti-neutrophilic cytoplasmic antibody (c ANCA and P ANCA), and complement levels. RESULTS: The study was performed in forty patients with severe or critical illness. The mean age of the participants was 48.5 ± 9.8 years. All patients had pulmonary involvement in lung computed tomography scans. Vasculitis laboratory test results included RF in two patients, ANA in three patients, and ANCA in one patient. Seventeen (42.5%) patients had hypocomplementemia in one or more complement tests. Four patients expired, of whom three had a decrease in complement level. CONCLUSION: Decrease in complement levels may predict a critical state of COVID-19 disease. Therefore, measuring its levels may be of great benefit in making earlier decisions to initiate disease-suppressing treatments including corticosteroids.

Seroconversion to antinuclear antibody negativity and its association with disease flare in patients with systemic lupus erythematosus.

OBJECTIVE: To evaluate the rate of seroconversion to antinuclear-antibody negativity in patients with systemic lupus erythematosus and its association with subsequent systemic lupus erythematosus flare risk. METHODS: Medical records of patients with systemic lupus erythematosus with positive antinuclear antibodies (titer ≥1 : 40) at diagnosis and at least one repeat antinuclear antibody test were reviewed. We determined the frequency of seroconversion to antinuclear antibody negativity among these patients and investigated whether seroconversion to antinuclear antibody negativity was associated with subsequent systemic lupus erythematosus flare risk. The seroconversion to antinuclear antibody negativity was defined as a conversion of positive antinuclear antibodies to a titer below the cut-off of 1 : 40. Systemic lupus erythematosus flare was defined as one new British Isles Lupus Assessment Group A or two new British Isles Lupus Assessment Group B domain scores. To estimate hazard ratios and 95% confidence intervals for systemic lupus erythematosus flare according to seroconversion to antinuclear antibody negativity, Cox regression analysis with adjustment for known systemic lupus erythematosus flare risk factors was performed. Kaplan-Meier analysis was used to compare flare-free survival rates between negative converters and non-converters. RESULTS: Among the total 175 patients, seroconversion to antinuclear antibody negativity was found in 17 (9.7%) patients in a median 53.5 (range: 25.7-84.0) months. After the last antinuclear antibody tests, 53 systemic lupus erythematosus flare cases were identified during 14.3 (range: 8.2-21.7) months of follow-up. Systemic lupus erythematosus flare risk was significantly lower in patients with negatively seroconverted antinuclear antibodies (adjusted hazard ratio 0.13, 95% confidence interval 0.03-0.58, p = 0.007). Kaplan-Meier analysis showed significantly higher flare-free survival in negative converters than in non-converters (p = 0.004). CONCLUSION: Seroconversion to antinuclear antibody negativity occurred in 9.7% of patients over 53.5 months and was associated with a lower future systemic lupus erythematosus flare risk.