Antinuclear Antibody Titer Research Articles

Undifferentiated Connective Tissue Disease and Interstitial Lung Disease: Trying to Define Patterns

ObjectivesTo identify clinical or immunological features in patients with undifferentiated connective tissue disease (UCTD) associated interstitial lung disease (ILD), in order to group them and recognize different functional and high resolution computed tomography (HRCT) behavior. MethodsRetrospective cohort study. Patients meeting Kinder criteria for UCTD were included. We defined the following predictive variables: ‘highly specific’ connective tissue disease (CTD) manifestations (Raynaud's phenomenon, dry eyes or arthritis), high antinuclear antibody (ANA) titer (above 1:320), and ‘specific’ ANA staining patterns (centromere, cytoplasmic and nucleolar patterns). We evaluated the following outcomes: change in the percentage of the predicted forced vital capacity (FVC%) during the follow-up period, and HRCT pattern. ResultsSixty-six patients were included. Twenty-nine (43.94%) showed at least one ‘highly specific’ CTD manifestation, 16 (28.57%) had a ‘specific’ ANA staining pattern and 29 (43.94%) high ANA titer. Patients with ‘highly specific’ CTD manifestations were younger (mean [SD] 52 years [14.58] vs 62.08 years [9.46], P<.001), were more likely men (10.34% vs 48.65%, P<.001) and showed a smaller decline of the FVC% (median [interquartile range] 1% [−1 to 10] vs −6% [−16 to −4], P<.006). In the multivariate analysis, the presence of highly specific manifestations was associated with improvement in the FVC% (B coefficient of 13.25 [95% confidence interval, 2.41 to 24.09]). No association was observed in relation to the HRCT pattern. ConclusionThe presence of ‘highly specific’ CTD manifestations was associated with female sex, younger age and better functional behavior. These findings highlight the impact of the clinical features in the outcome of patients with UCTD ILD.

Ten‐year retrospective clinicohistological study of cutaneous lupus erythematosus in Korea

An understanding of the differences in clinical manifestations and laboratory abnormalities between subtypes of cutaneous lupus erythematosus (CLE) is still lacking. The purpose of this study was to analyze demographic, clinical and histological features of CLE according to three main presentation subsets: acute (ACLE), subacute (SCLE) and chronic (CCLE). A 10-year retrospective analysis was performed on data from patients who were diagnosed with CLE between March 2005 and September 2015 in a Korean tertiary referral dermatology clinic. We compared demographic data and clinical and histological findings between three different CLE groups. An overall sample of 220 patients with CLE consisted of 67 patients with ACLE, 25 patients with SCLE and 135 patients with CCLE. Patients with CCLE regardless of systemic lupus erythematosus (SLE) presence had lower prevalence of anemia, urinary abnormalities and elevated erythrocyte sedimentation rate. Furthermore, CCLE patients who only had skin lesions showed lower female predominance, lower extracutaneous manifestation, fewer laboratory and immunological abnormalities including low antinuclear antibody titers and the lowest positivity for C3, C4 and anti-dsDNA, anti-Ro, anti-Sm and anti-RNP antibodies, and more prominent perieccrine inflammation and dermal fibrosis in histological findings. Considering distinct cutaneous manifestations of LE, a comprehensive awareness of each CLE subtype is important for achieving a favorable prognosis through appropriate diagnosis and management. This study provides comparative clinical and histological profiles of patients with different CLE subtypes in Korea.

N-acetylcysteine exposure is associated with improved survival in anti-nuclear antibody seropositive patients with usual interstitial pneumonia

BackgroundMortality is similarly high among individuals with usual interstitial pneumonia (UIP) due to idiopathic pulmonary fibrosis (IPF) and interstitial pneumonia with autoimmune features (IPAF). Circulating anti-nuclear antibodies (ANA) are commonly found in this patient population, suggesting possible aberrant immune activation. Because an environment of oxidative stress can result from immunologic activation, we hypothesized that ANA positive patients with UIP would have improved outcome when exposed to the antioxidant N-acetylcysteine (NAC) compared to ANA negative patients.MethodsA single center, retrospective cohort analysis was performed. Patients with UIP due to IPF and IPAF were stratified according to ANA status to and NAC exposure. Transplant-free survival (TFS) was assessed using the Kaplan-Meier estimator and multivariable Cox regression adjusted for diagnosis, gender/age/physiology score, immunosuppressant exposure and anti-fibrotic exposure.ResultsOf 293 individuals with UIP due to IPF (74%) or IPAF (26%), NAC exposure was documented in 58 (19.8%). Among NAC exposed individuals, 33 (56.9%) were ANA seropositive and 25 (43.1%) were seronegative. NAC exposure was associated with improved TFS survival among ANA seropositive individuals in unadjusted analysis (plogrank = 0.02) and after multi-variable adjustment (HR 0.51, 95% CI 0.30–0.87; p = 0.01). There was no association between NAC exposure and TFS in ANA seronegative individuals (HR 1.26, 95% CI 0.69–2.32; p = 0.45). Formal interaction testing confirmed NAC*ANA interaction (p = 0.04) and sensitivity analysis demonstrated an increasing effect size associated with NAC therapy as ANA titer increased. Among patients with available genetic data, a marginally higher proportion of ANA positive patients (p = 0.08) carried the rs3750920 (TOLLIP) genotype previously shown to predict favorable outcome in NAC exposed patients.ConclusionNAC exposure is associated with improved transplant-free survival ANA positive patients with UIP. These findings support the prospective collection of ANA data in in future NAC clinical trials performed in patients with UIP.

Clinical features of chronic relapsing inflammatory optic neuropathy

Objective: To explore the clinical characteristics and prognosis of chronic relapsing inflammatory optic neuropathy (CRION). Methods: A retrospective analysis was conducted. Clinical features, disease course, prognosis and magnetic resonance imaging (MRI) of patients with CRION who were admitted to Department of Neurology between 2014 and 2016 were reviewed and analyzed. Results: Totally, there were 27 patients (10 males and 17 females), with an age range of 17-59 years. The disease duration was between 40 days and 8 years. There were 2 to 9 CRION episodes. The mean frequency of CRION episodes was 3.30±1.56. The outcome of visual acuity showed that the more episodes frequency was, the worse outcome became. There was 25 abnormal optic nerve signals in MRI. And in 22 cases, the abnormal signals were in intraorbital segment or inner pipe section. The antinuclear antibodies (ANA) titers were elevated in 5 patients. Five cases relapsed during reduction or withdrawal of steroids, but steroids was not added in time. The final outcome of these 5 patients was poor. Conclusions: CRION was more common in female than male patients. Most patients were companied by pain, and the lesions were more common in the intraorbital segment of optic nerve. The more episode frequency was, the worse prognosis became. If a relapse happened, steroids or other immunosuppressive agents should be used.

Thank God for Lab: Systemic Lupus Erythematosus - A Difficult Diagnosis, a Difficult Disease

Abstract Systemic Lupus Erythematosus (SLE) involves autoimmune mechanisms that affect multiple systems and has variable clinical manifestations. It affects mainly feminine gender, usually of child-bearing age. Very late onset SLE (patients older than 75 years) is rarely met and difficult to diagnose due to the unspecific symptoms. The diagnosis is frequently mistaken for drug-induced SLE or for other age-specific disorders. We present the case of a 78 years old male patient complaining of hemoptysis in small amounts, fever, dyspnea at small efforts, weight loss, and important asthenia. Based on physical examination, severe anemia and thoracic CT aspect, several diagnosis were taken into account: anemic syndrome and pleurisy due to refractory pneumonia, pulmonary neoplasm, pulmonary tuberculosis, congestive heart failure and Wegener granulomatosis. Only when direct Coombs test came positive and all the other serological tests resulted negative, diagnosis of SLE was considered. Confirmation came along with high titers of antinuclear antibodies, anti double strained DNA antibodies and lupic anticoagulant and low levels of C3c and C4. We conclude that the diagnosis of SLE must be taken into consideration even in elder male patients. Therapeutic options in these patients are challenging because of the associated comorbidities and side effects.

Performance of Antinuclear Antibodies for Classifying Systemic Lupus Erythematosus: A Systematic Literature Review and Meta-Regression of Diagnostic Data.

To review the published literature on the performance of indirect immunofluorescence (IIF)-HEp-2 antinuclear antibody (ANA) testing for classification of systemic lupus erythematosus (SLE). A systematic literature search was conducted in the Medline, Embase, and Cochrane databases for articles published between January 1990 and October 2015. The research question was structured according to Population, Intervention, Comparator, Outcome (PICO) format rules, and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations were followed where appropriate. Meta-regression analysis for diagnostic tests was performed, using the ANA titer as independent variable, while sensitivity and specificity were dependent variables. Of 4,483 publications screened, 62 matched the eligibility criteria, and another 2 articles were identified through reference analysis. The included studies comprised 13,080 SLE patients in total, of whom 12,542 (95.9%) were reported to be IIF-ANA positive at various titers. For ANA at titers of 1:40, 1:80, 1:160, and 1:320, meta-regression gave sensitivity values of 98.4% (95% confidence interval [95% CI] 97.6-99.0%), 97.8% (95% CI 96.8-98.5%), 95.8% (95% CI 94.1-97.1%), and 86.0% (95% CI 77.0-91.9%), respectively. The corresponding specificities were 66.9% (95% CI 57.8-74.9%), 74.7% (95% CI 66.7-81.3%), 86.2% (95% CI 80.4-90.5%), and 96.6% (95% CI 93.9-98.1%), respectively. The results of this systematic literature review and meta-regression confirm that IIF-ANAs have high sensitivity for SLE. ANAs at a titer of 1:80 have sufficiently high sensitivity to be considered as an entry criterion for SLE classification criteria, i.e., formally test other classification criteria for SLE only if ANAs of at least 1:80 have been found.

Prevalence of antinuclear and anti-erythrocyte antibodies in healthy cats.

Positive antinuclear antibody and direct antiglobulin tests support diagnoses such as systemic lupus erythematosus and immune-mediated anemia, respectively. Positive tests may occur in cats, but the prevalence of positive results in healthy cats is not well known. The study's purpose was to determine prevalences of positive antinuclear antibody and direct antiglobulin tests in healthy cats. Antinuclear antibody titers were measured by indirect immunofluorescence, and anti-erythrocyte antibodies were measured by the microtitration direct antiglobulin test at 37, 23, and 4°C in 61 client-owned and 28 facility-owned cats. Differences between the 2 groups were examined using chi-squared tests. For the antinuclear antibody tests, 70% of client-owned cats were negative, 10% had weak titers (1:40-1:80), and 20% had strong titers (1:160-1:320). Facility-owned cats had significantly fewer positive titers with 96% negative and one positive (1:8). For the antiglobulin test at 37°C, 93% of all cats were negative, 2 cats in each group were positive at low dilutions (1:2), and 2 client-owned cats were transiently positive at high dilutions (≥1:2048). At 23°C, 90% of all cats were negative, and 2 client-owned and 5 facility-owned cats were positive at low dilutions (1:2-1:8). At 4°C, 67% of client-owned cats had invalid results (negative control well agglutination), and 33% had negative results, while of facility-owned cats 14% had invalid results, 14% had agglutination at low dilutions, and 72% were negative. Healthy cats may have positive antinuclear antibody and direct antiglobulin tests, but the prevalence of strong reactions is low.

Scabies presenting as cutaneous nodules or malar erythema: reports of patients with scabies surrepticius masquerading as prurigo nodularis or systemic lupus erythematosus

Scabies surrepticius is a unifying term that represents non-classical presentations of scabies mite infestation. A patient with scabies surrepticius is described: a man with scabies masquerading as prurigo nodularis. The 91-year-old man had metastatic prostate cancer and presented with diffuse pruritic nodules. Prurigo nodularis was suspected; however, the biopsy revealed scabies mites in the stratum corneum. He was successfully treated with topical permethrin 5% cream and oral ivermectin. In addition, the features of a woman with scabies mimicking systemic lupus erythematosus are summarized. The 47-year-old woman had idiopathic thrombocytopenic purpura and presented with malar erythema and a positive antinuclear antibody (titer 1:320). A diagnosis of systemic lupus erythematous was entertained until skin scraping and mineral oil preparation revealed scabies mites; she was successfully treated with oral ivermectin. In conclusion, Sarcoptes scabiei infestation can present with atypical clinical morphology and an absence of classical lesions such as burrows conventionally distributed in the interdigital web spaces, volar wrists, periumbilical area, or genitalia. Scabies surrepticius is a term that has been designated to describe these unusual presentations. Prurigo nodularis and systemic lupus erythematosus can be added to the litany of conditions masquerading as scabies and are included amongst the guises of scabies surrepticius.

Determination of Specificity and Pattern of Antinuclear Antibodies (ANA) in Systemic Rheumatic Disease Patients Positive for ANA Testing.

To determine probability of finding antinuclear antibodies (ANA) and anti extractable nuclear antigens (ENA) positive samples and associating ANA patterns with anti-ENA reactivities among a consecutive cohort of samples of systemic rheumatic disease patients referred for ANA testing. Prospective cohort study. Immunology Department, Armed Forces Institute of Pathology, Rawalpindi, Pakistan, from January to June 2016. All the samples referred for ANA testing with clinical suspicion of systemic rheumatic disease were included. After screening, ANA positive samples were subjected to anti-ENA antibodies testing (including anti-SSA, antiSSB, anti-Sm, anti-RNP, anti-SCL-70 and anti-Jo-1 antibodies) and ANA pattern and titer determination. Of 4,347 samples received, 397 were positive for ANA (9%). Of 397, 96 (24%) samples positive on ENA screen were tested for anti-ENA reactivity. Anti-SSA antibodies were found in 59 samples. Commonest ANA patterns were coarse and fine speckled (43 and 22 samples of 81 tested), while majority of samples carried ANA in titers of 1:40 and 1:80 (22 and 18 samples of 81 tested). No specific ANA pattern was associated with any particular anti-ENA reactivity. Among samples/patients referred for investigations of autoimmune disorders, probability of finding positive ANA is approximately 9%. Of these 9%, about 24% also show reactivity against ENA. Commonest ANA pattern is coarse speckled and majority of such patients carry ANA in titers ranging from 1:40 to 1:80. Commonest ENA reactivity was against SSA.

The evaluation of cellular immune function in elderly patients with systemic lupus erythematosus.

Background/AimsTo evaluate cellular immune function in systemic lupus erythematosus (SLE) patients over 60 years old, the association between antinuclear antibody (ANA) titers and the ratio of CD4+ /CD8+ was analyzed in this study. The distribution of ANAs and extractable nuclear antibodies (ENAs) in a healthy elderly population was also investigated.MethodsSerum ANA titers were assayed by indirect immunofluorescence (IIF) and the CD4+ /CD8+ T-cell ratio was determined by flow cytometry in 76 SLE patients and 30 healthy control individuals. IIF of cytoplasm and nuclear and nucleolar staining were performed on samples taken from 286 healthy elderly individuals. ENA levels were determined using a strip enzyme immunoassay among patients that tested positive for ANAs.ResultsANA titers were negative in the 30 control individuals, but were positive in the 76 SLE patients. Based on ANA titers, the SLE patients were stratified to low (≤ 1:320), medium (1:640 to 1:1,280), and high (≥ 1:2,560) titer groups. The average CD4+ /CD8+ ratio of the SLE group was significantly lower than that of the control group. Among the 286 healthy elderly volunteers, 59 (20.63%) tested positive for ANAs. A homogeneous pattern was present in 47.46% of those 59 patients and a granule pattern in the karyoplasm was present in 33.90%. Furthermore, of the 59 patients, ENAs immunoassay was positive in 18 (30.51%); Sjogren syndrome-related antigen A (SSA)/52 kd and Sjogren syndrome antigen B (SSB)/La were the two major antibodies.ConclusionsThe significantly lower CD4+ /CD8+ ratio among SLE patients over 60 years old is associated with deregulated immune responses and the development of SLE. A low ANA titer (1:160) is common in healthy elders, emphasizing the importance of considering age when determining if the evaluation of ANA titers is to be included in autoimmune disease diagnosis.

Hematoxylin Bodies in Pediatric Bone Marrow Aspirates and their Utility in the Diagnosis of Systemic Lupus Erythematosus.

In our recent case report, the finding of lupus erythematosus (LE) cells in a bone marrow aspirate led to the diagnosis of systemic lupus erythematosus (SLE) and appropriate treatment, although the patient was not clinically suspected to have SLE. To determine whether LE cells are present in the bone marrow aspirates of SLE patients, but overlooked in routine bone marrow morphology review, bone marrow aspirates from 30 pediatric patients (15 with SLE and 15 with other diagnoses) evaluated by rheumatologists were reviewed. LE cells were found in the bone marrow aspirates of only 1 SLE patient and none in non-SLE patients. However, hematoxylin bodies were identified in 53% (8/15) of SLE patients. Neither hematoxylin bodies nor LE cells were found in the aspirates from patients with other disorders. Three additional pediatric patients identified prospectively were found to have hematoxylin bodies in the bone marrow aspirates. Although the diagnosis was not initially suspected, 2 of the 3 patients were subsequently diagnosed with SLE. All patients with hematoxylin bodies and SLE had antinuclear antibody titers ≥1:640 with a homogeneous staining pattern. In addition, bone marrow aspirates of 9 adult patients were reviewed, and neither LE cells nor hematoxylin bodies were identified. In summary, hematoxylin bodies were present in the bone marrow aspirates of many pediatric SLE patients, while LE cells were rare. The finding of hematoxylin bodies in pediatric bone marrow aspirates is a helpful and specific diagnostic clue that may lead to the diagnosis of SLE when other clinical features are nonspecific.

Chondroitin Sulphate: Unmasking Autoimmune Hepatitis

Auto-immune hepatitis is a chronic liver condition characterized by the presence of immunologic features. Triggers for auto-immune hepatitis are hypothesized to be environmental factors, viruses, drugs and herbal supplements. Herein we present a case of auto-immune hepatitis unmasked by a chondroitin sulphate supplement. A 64 year old woman with persistent mildly elevated liver function tests (LFT's); Aspartate aminotransferase (AST) 36-114 U/L, alanine aminotransferase (ALT) 24-86 U/L and minimally elevated anti-nuclear antibody (ANA) and anti-smooth muscle antibody(ASMA)titers (1:40) was found to have a sudden increase in her LFT's during her 8th year of follow up. AST was 543 U/L, ALT 650 U/L, alkaline phosphatase 139 U/L, total bilirubin 1.4mg/dL, gamma-glutamyl transferase 285 U/L. One month prior to the office visit, the patient started taking a chondroitin supplement for knee osteoarthritis. Hepatitis serology, iron studies and auto-immune hepatitis workup was repeated which revealed negative viral hepatitis serology, normal iron studies and an increase in her anti-nuclear antibody titer(ANA) 1:2560, anti-smooth muscle antibody(ASMA) titer 1:160 and negative AMA. Abdominal ultrasound revealed mild coarse echotexture of the liver. Liver biopsy was performed which was suggestive of auto-immune hepatitis with moderate activity and cirrhosis (fig.1-2). International AIH score was 7 consistent with a definite diagnosis of AIH. Treatment with azathioprine and prednisone was started. In our patient the history of mildly elevated LFT's and positive ANA and ASMA indicate that the patient had a history of mild undiagnosed auto-immune hepatitis however the consumption of chondroitin sulphate unmasked her disease as evident by the sudden increase in LFT's, ANA and ASMA. Herbal preparations and supplements are often thought of as natural alternative remedies to medication without adverse effects. Chondroitin sulfate is a sulphated glycosaminoglycan and has become a widely used dietary supplement for treatment of osteoarthritis. Although it is a generally well tolerated dietary supplement, chondroitin sulphate has been reported to cause drug-induced liver injury in patients with chronic liver disease and even liver injury mimicking auto-immune hepatitis as reported previously. Supplements containing chondroitin sulphate may not be suitable for patients with chronic liver disease and may be associated with auto-immune hepatitis. Further investigation is warranted.Figure: Liver biopsy 20x. Portal triad with inflammation, interface hepatitis.Figure: Liver biopsy 40x. Mixed infiltrate plasma cells and lymphocytes.Figure: Trichrome stains showing bridging fibrosis with nodules. 10x.

Choosing wisely? Multiple Sclerosis and Laboratory Screening for Autoimmune Differential Diagnoses

Abstract Background A variety of diseases can mimic the presentation of multiple sclerosis (MS). Diagnosing MS requires the exclusion of conditions considered in the differential diagnosis of MS. The guidelines of the German Society of Neurology (DGN) recommend analyzing 13 mandatory and 9 optional laboratory parameters. The mandatory recommendations include antinuclear antibodies (ANA) as well as antibodies against double-stranded DNA (anti-dsDNA Abs)). Methods In a cohort of MS outpatients, those patient records were analyzed in which test results for all or at least some of the recommended laboratory parameters were available. In addition to these laboratory parameters, MRI data, family history, clinical presentation, evoked potentials, and CSF findings were analyzed. Furthermore, a questionnaire was used to prospectively collect information about rheumatological symptoms relevant to the differential diagnosis of MS. Results In 197 of the included 554 patients, at least some of the recommended differential diagnostic laboratory parameters were available. In 59.4% of these patients, ANA titers ≥ 1:80 were detected. Neither ANA nor ANCA nor anti-dsDNA abs were able to distinguish between MS and non-MS. In 124 MS patients, 54.8% had positive ANA titers ≥1:80. MS patients with these titers suffered more frequently from autoimmune diseases and were more likely to have a family history of MS. Of the remaining 73 patients without MS, 67.1% were ANA positive. In this patient population, the ANA-positive patients were more frequently diagnosed with psychiatric diseases. In the prospectively surveyed MS patients with an ANA titer &gt;1:160, no rheumatologic disease was diagnosed during the average follow-up period of 1.9 years. Conclusion In line with the "Choosing Wisely" recommendations of the American College of Rheumatology, mandatory laboratory screening appears to offer no benefit to the initial diagnosis of multiple sclerosis, unless a specific differential diagnosis is to be excluded.

Small Duct Primary Sclerosing Cholangitis

Primary sclerosing cholangitis (PSC) is a well documented disease of the biliary tract associated with inflammatory bowel diseases (IBD), especially ulcerative colitis.1 Small-duct PSC, a variant of PSC, also has an association with inflammatory bowel disease.1 The exact pathogenesis of PSC is not well understood, but thought to be due to a combination of a genetic predisposition and gut structure.1 A 34 year-old male with a history significant for rheumatoid arthritis, portal vein thrombosis and ulcerative colitis presented to the hepatology clinic for evaluation of abnormal liver enzymes. He was diagnosed with ulcerative colitis at age 24 and over the years treated with Mesalamine, steroids, Azathioprine, Cyclosporine, and Infliximab. However, he was unresponsive to therapy and underwent total colectomy 2 years after diagnosis. The liver enzymes of concern had a mixed cholestatic and hepatocellular pattern with ALT 203, AST 104, Tbili 1.7, Dbili 0.6, and ALP 339. Hence, the differential was initially broad including possible autoimmune causes, vascular with the portal vein thromboses history, drug induced or primary sclerosing cholangitis (PSC) or primary biliary cirrhosis. A viral hepatitis screen was negative. Autoimmune testing revealed a positive anti-nuclear antibody titer. Magnetic resonance cholangiopancreatography (MRCP) revealed hypoattenuations correlating with his history of portal vein thromboses. Liver biopsy revealed small duct PSC. He is scheuled for imaging every 6 months to observe for cholangitis. A retrospective analysis of patients with PSC from 1980 to 2010 at 37 centers in Europe, North America, and Australia was completed by the International PSC Study Group.2 Of the 7121 patients, 65.5% were men, 89.8% had classical or large-duct disease, and 70.0% developed IBD at some point.2 Small-duct PSC was associated with a lower risk of liver transplant, death or malignancy compared with classic PSC.2 Small-duct PSC characterized a low-risk phenotype in both sexes.2 This suggests that small duct PSC is usually seen in younger individuals, in early stage disease, and suggests better outcomes.

Immune intervention with anti-CD80 bivalent antibody in pristane-induced mouse model of lupus nephritis

Objective To study the therapeutic effect of anti-CD80 bivalent antibody on mouse lupus nephritis and to explore the possible molecular mechanism. Methods A mouse model of lupus nephritis was established through intraperitoneal injection of 0.5 ml of pristine in female C57BL/6J mice. Appearance of urinary protein and significantly increased levels of peripheral antinuclear antibody (ANA) and anti-double-stranded DNA (anti-dsDNA) antibody in the fourth month after injection indicated that the mouse model was established successfully. Then the mice were divided into two groups including anti-CD80 bivalent antibody intervention group (injected with 200 μg of anti-CD80 bivalent antibody at day 1, 3, 5, 8 and 15, followed by three times of injection with an interval of one month) and model group (injected with the same protein using the same strategy). A normal control group was set up accordingly. Albustix test paper was used to monitor the dynamic changes in mouse urinary protein. Flow cytometry was used to analyze the activation of immune-related cells in spleen. Levels of autoantibodies (ANA and anti-dsDNA) and levels of IFN-γ and IL-4 in serum were detected by indirect immunofluorescence assay. Renal tissue samples were analyzed with hematoxylin and eosin (HE) staining and immunocomplex (IC) assay. Results Urinary protein level of the anti-CD80 bivalent antibody intervention group was significantly lower than that of the model group (P<0.05). Activated macrophages, dendritic cells, neutrophils and B cells in spleen tissues of the anti-CD80 bivalent antibody intervention group were significantly less than those of the model group (P<0.05), and the numbers of CD4+ and CD154+ T cells were significantly less than those of the model group (P<0.05). Positive rates and titers of ANA and dsDNA in serum samples of the intervention group were lower than those of the model group (P<0.05). Levels of IFN-γ and IL-4 in serum samples of the intervention group were decreased as compared with those of the model group (P<0.05). HE staining and immunofluorescence assay showed that glomerular inflammatory injury and necrosis were alleviated and kidney immune complex deposition was reduced after anti-CD80 bivalent antibody intervention. Conclusion Anti-CD80 bivalent antibody specifically binds to the CD80 molecule on antigen presenting cell surface, blocks the CD80/CD28 co-stimulatory signaling pathway and down-regulates the body′s immune response, which alleviates and reverses the lupus-like nephritis-induced pathological damages in mice. Key words: Bivalent antibody; CD80; Co-stimulatory signals; Lupus nephritis; Pathological damage

Phenotypic Clusters Predict Outcomes in a Longitudinal Interstitial Lung Disease Cohort

The current interstitial lung disease (ILD) classification has overlapping clinical presentations and outcomes. Cluster analysis modeling is a valuable tool in identifying distinct clinical phenotypes in heterogeneous diseases. However, this approach has yet to be implemented in ILD. Using cluster analysis, novel ILD phenotypes were identified among subjects from a longitudinal ILD cohort, and outcomes were stratified according to phenotypic clusters compared with subgroups according to current American Thoracic Society/European Respiratory Society ILD classification criteria. Among subjects with complete data for baseline variables (N= 770), four clusters were identified. Cluster 1 (ie, younger white obese female subjects) had the highest baseline FVC and diffusion capacity of the lung for carbon monoxide (Dlco). Cluster 2 (ie, younger African-American female subjects with elevated antinuclear antibody titers) had the lowest baseline FVC. Cluster 3 (ie, elderly white male smokers with coexistent emphysema) had intermediate FVC and Dlco. Cluster 4 (ie, elderly white male smokers with severe honeycombing) had the lowest baseline Dlco. Compared with classification according to ILD subgroup, stratification according to phenotypic clusters was associated with significant differences in monthly FVC decline (Cluster 4, -0.30%vsCluster 2, 0.01%; P< .0001). Stratification by using clusters also independently predicted progression-free survival (P<.001) and transplant-free survival (P< .001). Among adults with diverse chronic ILDs, cluster analysis using baseline characteristics identified four distinct clinical phenotypes that might better predict meaningful clinical outcomes than current ILD diagnostic criteria.

Autoimmune phenotype with type I interferon signature in two brothers with ADA2 deficiency carrying a novel CECR1 mutation

BackgroundLoss-of-function CECR1 mutations cause polyarteritis nodosa (PAN) with childhood onset, an autoinflammatory disorder without significant signs of autoimmunity. Herein we describe the unusual presentation of an autoimmune phenotype with constitutive type I interferon activation in siblings with adenosine deaminase 2 (ADA2) deficiency.Case presentationWe describe two siblings with early-onset recurrent strokes, arthritis, oral ulcers, discoid rash, peripheral vascular occlusive disease and high antinuclear antibody titers. Assessment of interferon signatures in blood revealed constitutive type I interferon activation. Aicardi-Goutières syndrome (AGS) was suspected, but no mutation in the known AGS genes were detected. Whole exome sequencing identified compound heterozygosity for a known and a novel mutation in the CECR1 gene. Functional consequences of the mutations were demonstrated by marked reduction in ADA2 catalytic activity.ConclusionsOur findings demonstrate that ADA2 deficiency can cause an unusual autoimmune phenotype extending the phenotypic spectrum of PAN. Constitutive interferon I activation in patient blood suggests a possible role of type I interferon in disease pathogenesis which may have therapeutic implications.

Seropositivity and Titers of Anti-Smooth Muscle Actin Antibody Are Associated with Relapse of Type 1 Autoimmune Hepatitis.

BackgroundIt is important to avoid relapse in autoimmune hepatitis (AIH) because repeated multiple relapses have been associated with a worse prognosis. However, risk factors for relapse before initiation of treatment are not fully understood. The aim of this study was to find predictive markers for relapse of type 1 AIH.Material/MethodsWe reviewed the records of 53 patients diagnosed with type 1 AIH based on the revised scoring system proposed by the International Autoimmune Hepatitis Group (IAIHG) between 2009 and 2014 at 4 hospitals belonging to the Saga Study Group of Liver Diseases (SASLD). We analyzed the differences in background characteristics between patients with or without relapse.ResultsAll patients achieved remission after treatment, and 9 (17%) subsequently relapsed. The relapsed patients were significantly younger and had a higher positive rate of anti-smooth muscle antibody (ASMA) than the non-relapsed patients (100% vs. 25%, P=0.0012). Moreover, relapse rate increased with titer of ASMA, while titer of antinuclear antibody was not associated with relapse rate.ConclusionsASMA is a useful predictive marker for relapse of type 1 AIH during or after withdrawal of medical therapy. More careful attention should be paid to immunosuppressive therapy in patients with high titers of ASMA.

Urticarial Reaction to Ustekinumab During the Treatment of Plaque Psoriasis in a Hepatitis C-Positive Patient.

A 62-year-old white woman with a history of hepatitis C and type 2 diabetes mellitus developed urticaria during treatment with ustekinumab for plaque psoriasis. The patient received two 45-mg ustekinumab injections in her first 2 months and then one 45-mg injection every 3 months for her psoriasis. After 10 months, she developed a round red rash on her skin diffusely on her body. She also complained of joint pain in her hands. Rheumatology became involved, and investigations revealed that her antinuclear antibody titer was negative, but her rheumatoid factor, erythrocyte sedimentation rate, and liver function enzymes were elevated. She was diagnosed with urticaria, and ustekinumab was discontinued. A Naranjo assessment score of 6 was obtained, indicating a probable relationship between the patient’s urticaria and her use of ustekinumab. Ustekinumab was subsequently discontinued, and the patient received a course of Harvoni® (Gilead Sciences, Inc., Forest City, California, United States) (ledispasvir/sofosbuvir) with clearance of the hepatitis C virus. The patient is currently receiving another biologic agent, ixekizumab, and reports no complaints, including that of urticaria.

Intracranial lesion as onset symptom in a patient with early undifferentiated connective tissue disease: a case report

BackgroundUndifferentiated connective tissue disease (UCTD) is widely considered to be a distinct clinical entity, and now divided into two subgroups: stable UCTD and early UCTD. The most frequent onset symptoms of UCTD include arthralgias, arthritis, Raynaud’s phenomenon, mucocutaneous involvement, and sicca symptoms. However, Neurologic involvement is rare, and intracranial lesion as onset symptom in a patient with early UCTD has not yet been reported.Case presentationA 51-year-old Chinese female experienced progressive left leg weakness for 14 days before hospitalizing in our department. The lesion on right parietal lobe was initially detected by brain magnetic resonance imaging. Although the patient declined a cerebral biopsy, the possibility of stroke, cerebral venous sinus thrombosis, NMOSD, MS, autoimmune encephalitis, intracranial infections, and malignant tumors as cause of the lesion was excluded by intracranial angiogram, CSF study, MRI enhancement and MRS examination. Moreover, immunologic studies showed high titer of antinuclear antibody, increased erythrocyte sedimentation rate and C-reactive protein. These results led to a diagnosis of early UCTD with central nerve system (CNS) involvement. After low dose corticosteroid and azathioprine therapy, the patient’s symptoms, abnormalities in immunologic tests and cerebral radiologic examinations were all greatly improved within a short duration.ConclusionsThis is the first report of intracranial lesion as onset symptom in a patient with early UCTD. Our case suggested that central nerve system (CNS) involvement could be the onset symptom in early UCTD, and should be recognized quickly with exclusion of other causative factors in the differential diagnosis. Prompt and adequate treatment with low-dose steroid and immunosuppressive drugs could improve the prognosis of both early UCTD and CNS involvement.