Agreement between local and central anti-synthetase antibodies detection: results from the Classification Criteria of Anti-Synthetase Syndrome project biobank.

OBJECTIVES: The CLASS (Classification Criteria of Anti-Synthetase Syndrome) project is a large international multicentre study that aims to create the first data-driven anti-synthetase syndrome (ASSD) classification criteria. Identifying anti-aminoacyl tRNA synthetase antibodies (anti-ARS) is crucial for diagnosis, and several commercial immunoassays are now available for this purpose. However, using these assays risks yielding false-positive or false-negative results, potentially leading to misdiagnosis. The established reference standard for detecting anti-ARS is immunoprecipitation (IP), typically employed in research rather than routine autoantibody testing. We gathered samples from participating centers and results from local anti-ARS testing. As an "ad-interim" study within the CLASS project, we aimed to assess how local immunoassays perform in real-world settings compared to our central definition of anti-ARS positivity. METHODS: We collected 787 serum samples from participating centres for the CLASS project and their local anti-ARS test results. These samples underwent initial central testing using RNA-IP. Following this, the specificity of ARS was reconfirmed centrally through ELISA, line-blot assay (LIA), and, in cases of conflicting results, protein-IP. The sensitivity, specificity, positive likelihood ratio and positive and negative predictive values were evaluated. We also calculated the inter-rater agreement between central and local results using a weighted κ co-efficient. RESULTS: Our analysis demonstrates that local, real-world detection of anti-Jo1 is reliable with high sensitivity and specificity with a very good level of agreement with our central definition of anti-Jo1 antibody positivity. However, the agreement between local immunoassay and central determination of anti-non-Jo1 antibodies varied, especially among results obtained using local LIA, ELISA and "other" methods. CONCLUSIONS: Our study evaluates the performance of real-world identification of anti-synthetase antibodies in a large cohort of multi-national patients with ASSD and controls. Our analysis reinforces the reliability of real-world anti-Jo1 detection methods. In contrast, challenges persist for anti-non-Jo1 identification, particularly anti-PL7 and rarer antibodies such as anti-OJ/KS. Clinicians should exercise caution when interpreting anti-synthetase antibodies, especially when commercial immunoassays test positive for non-anti-Jo1 antibodies.

Outcomes in progressive systemic sclerosis treated with autologous hematopoietic stem cell transplantation compared with combination therapy.

OBJECTIVES: Autologous hematopoietic stem cell transplantation (AHSCT) has been shown to improve long-term survival for early diffuse progressive systemic sclerosis (SSc) compared with cyclophosphamide. Cyclophosphamide, however, does not provide a long-term benefit in SSc. The combination of mycophenolate mofetil (MMF) and rituximab is a potent alternative regimen. We aimed to retrospectively compare the outcomes of SSc patients who underwent AHSCT to patients who met the eligibility criteria for AHSCT but received upfront combination therapy with MMF and rituximab. METHODS: Repeated assessments of modified Rodnan Skin Score (mRSS), forced vital capacity (FVC), and diffusing capacity (DLCO) values were conducted. Clinical improvement was defined as an mRSS decrease > 25% or an FVC increase > 10%. Event-free survival (EFS) was defined in the absence of persistent major organ failure or death. RESULTS: Twenty-one SSc patients in the combination therapy group were compared with sixteen in the AHSCT group. Age, sex and disease duration were similar between the two groups. Clinical improvement at 12 months was seen in 18 (86%) patients in the combination group compared with 13 (81%) in the AHSCT group (p= 0.7). The hazard ratio for EFS at 24 months favored the combination group (HR = 0.09, P= 0.04). During follow-up, both groups exhibited a significant and comparable reduction in mRSS and an increase in FVC values at each time interval up to 24 months. CONCLUSION: MMF and rituximab compared with AHSCT in SSc patients eligible for AHSCT resulted in similar skin and lung clinical improvement with a better safety profile at 24 months.

Urine soluble triggering receptor expressed on myeloid cells-1 is a novel biomarker for active lupus nephritis: a case-control study.

OBJECTIVES: To determine the value of plasma and urine sTREM-1 levels as a biomarker of lupus nephritis (LN) as well as extra-renal systemic lupus erythematosus (SLE). METHODS: Consecutive adult patients with SLE attending a tertiary lupus clinic in 2016-2018 were prospectively divided into 3 groups according to SLEDAI-2K and renal-SLEDAI scores: active renal lupus (ARL), active non-renal lupus (ANL), and inactive lupus (IL). Blood and spot urine samples from each group and matched healthy subjects were analysed by means of ELISA for plasma and urine sTREM-1 levels. RESULTS: The cohort included 59 patients (mean age 41.5+2.9 years, 85% female) with SLE: 15 ARL, 14 ANL, and 30 IL. The ARL group had higher scores on the SLEDAI-2K and renal-SLEDAI, and higher urine protein/creatinine ratio than the other patient groups (p=0.0001 for all). Plasma sTREM-1 level was highest in the ANL group (p=0.0085). Urine sTREM-1 level was higher in the whole SLE cohort than the healthy controls (p=0.0249), and higher in the ARL group than the others (p=0.0044). Neither plasma nor urine sTREM-1 level was associated with non-renal SLE features. On Spearman correlation analysis, urine sTREM-1 level, but not plasma sTREM-1 level, was correlated positively with renal-SLEDAI score (r=0.34, p=0.018), inversely with serum C3 and C4 levels (r=-0.42, p=0.0027 and r=-0.28, p=0.056, respectively), and positively with proteinuria (UPCR: r=0.32, p=0.0305). CONCLUSIONS: Urine sTREM-1 might serve as a potential biomarker of active renal SLE.

The Effect of Different Ethnic Origins in Israel on the Clinical Manifestations and Outcomes of Systemic Lupus Erythematous.

BACKGROUND: Epidemiological studies have shown a connection between ethnic origin and the incidence and outcome of systemic lupus erythematosus (SLE). OBJECTIVES: To evaluate the SLE outcomes among Ashkenazi Jews, non-Ashkenazi Jews, and Arabs. METHODS: We conducted a retrospective study of patients who were diagnosed with SLE and followed in lupus clinics at two large tertiary medical centers. The data were obtained from patient medical records. Patients were stratified into three ethnic origins: Ashkenazi Jews, non-Ashkenazi Jews, and Arabs. The primary outcomes were all-cause mortality, development of end-stage kidney disease (ESKD), and Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) 2K ≤ 4 at last visit. RESULTS: We included 570 patients in this study. The Arab group showed the highest number of SLE classification criteria at diagnosis and last encounters compared to non-Ashkenazi and Ashkenazi Jewish groups (6.0 vs. 5.0 and 4.0, respectively at diagnosis, P < 0.001; 8.0 vs. 7.0 and 6.0 at last visit, P = 0.01). In multivariate models, Arab patients had three times higher risk of all-cause mortality than Ashkenazi Jews (hazard ratio 2.99, 95% confidence interval [95%CI] 1.32-6.76, P = 0.009). ESKD was similar among the study groups. Low disease activity (SLEDAI 2K ≤ 4) at last visit was lower in the Arab group than the Ashkenazi Jews (odds ratio 0.50, 95%CI 0.28-0.87, P = 0.016), depicting a medium-to-high disease activity among the former. CONCLUSIONS: Physicians should consider the influence of the ethnicity of the SLE patient when deciding on their care plan.

Lower socioeconomic status worsens outcome of patients with systemic lupus erythematosus independently of access to healthcare.

OBJECTIVES: Socioeconomic status (SES) has been found to be associated with worse outcomes of systemic lupus erythematosus (SLE). The impact of national health insurance on SLE outcomes has not been explored. METHODS: A retrospective inception cohort of patients older than 18 years with SLE diagnosed and followed in lupus clinics of two large tertiary medical centers were included. Patients were stratified into three groups by SES: lower 25th quantile, middle 25th-75th quantile, and upper 75th quantile. Primary outcomes were all-cause mortality, development of end-stage kidney disease (ESKD), and score ≤ 4 on the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI 2K) at the last visit. RESULTS: We identified 617 patients (548 females, 88.8%) with a median follow-up of 15 years (range, 8.0-23.0). Compared to the middle and upper SES groups, the lower SES group was characterized by younger age at disease onset (31.5 years vs. 34.3 and 37.4 years, respectively, p = 0.011) and higher rate of lupus nephritis (42.7% vs. 35.7% and 23.8%, respectively, p = 0.002). In multivariate models, patients in the middle and upper SES groups had a significantly lower risk of mortality (HR = 0.45; 95% CI, 0.24-0.82, p = 0.010) and ESKD (HR = 0.24; 95% CI, 0.08-0.73, p = 0.012), with no effect on the rate of SLEDAI 2K ≤ 4 (OR = 1.49; 95% CI, 0.92-2.40, p = 0.09). CONCLUSION: Even within a health system that provides high and equal accessibility to medical care, low SES is associated with worse outcomes of SLE. Policymakers should focus on managing possible barriers that prevent patients of lower SES from obtaining optimal care.

Anti-Ro/SS-A antibody is associated with worse pulmonary outcome and reduced overall survival in systemic sclerosis.

OBJECTIVE: We sought to determine the association of anti-Ro/SS-A antibody with organ involvement and disease outcome in patients with systemic sclerosis (SSc). METHODS: A retrospective, long-term study of a cohort of incident patients diagnosed with SSc and continuously followed at our rheumatology clinic during 1990-2018. RESULTS: Included were 105 patients with known anti-Ro/SS-A antibody status, 92.4% female, mean age at diagnosis 52.0 ± 15.6 years, and median follow-up of 10 years; 64% were diagnosed with limited cutaneous SSc, 18% with diffuse cutaneous SSc, and 18% had SSc siné scleroderma or undetermined disease type. Anti-Ro/SS-A antibody tested positive in 21% of patients. In univariate analysis, anti-Ro/SS-A antibody positivity was significantly associated with SSc overlap with Sjögren's syndrome (p < .001). Predicted forced vital capacity deterioration at last encounter was significantly associated with anti-Ro/SS-A antibody positivity. In multivariate regression for anti-Ro/SS-A antibody-positive SSc patients and disease outcome [adjusted for age > 50 years, smoking, and baseline predicted forced vital capacity (pFVC) < 80%], positive anti-Ro/SS-A antibody was significantly associated with a higher all-cause mortality rate (HR 5.17, CI 95%, 1.18-22.67, p = .029), and greater deterioration of pFVC defined as a decrement of last available pFVC compared to first available pFVC of ≥10% (HR 3.65, CI 95%, 1.07-12.38, p = .038). CONCLUSIONS: Anti-Ro/SS-A antibody is an independent risk factor for worse pulmonary outcome and higher all-cause mortality in patients with SSc.

Hematological Manifestations among Patients with Rheumatic Diseases.

BACKGROUND: Rheumatic diseases have many hematological manifestations. Blood dyscrasias and other hematological abnormalities are sometimes the first sign of rheumatic disease. In addition, novel antirheumatic biological agents may cause cytopenias. SUMMARY: The aim of this review was to discuss cytopenias caused by systemic lupus erythematosus and antirheumatic drugs, Felty's syndrome in rheumatoid arthritis, and autoimmune hemolytic anemia, thrombosis, and thrombotic microangiopathies related to rheumatological conditions such as catastrophic antiphospholipid syndrome and scleroderma renal crisis. Key Message: The differential diagnosis of various hematological disorders should include rheumatic autoimmune diseases among other causes of blood cell and hemostasis abnormalities. It is crucial that hematologists be aware of these presentations so that they are diagnosed and treated in a timely manner.

Elevated Plasma Soluble Triggering Receptor Expressed on Myeloid Cells-1 Level in Patients with Acute Coronary Syndrome (ACS): A Biomarker of Disease Severity and Outcome.

BACKGROUND AND AIMS: Plasma levels of soluble triggering receptor expressed on myeloid cells (sTREM-1) reflect innate immune cell activation. We sought to evaluate sTREM-1 levels in patients with acute coronary syndrome (ACS) and their predictive value for disease severity and outcome. METHODS: Plasma sTREM-1 levels were prospectively measured by ELISA in 121 consecutive patients with new-onset (≤24 h) chest pain at arrival to the emergency department (ED) and 73 healthy controls. Secondary endpoints were the association of plasma levels of sTREM-1 with day 30 and month 6 major adverse cardiovascular events (MACE) defined as death, ACS, stroke, and need for coronary revascularization, as well as with CAD severity. The primary endpoint of the study was the association of plasma sTREM-1 level at the time of admission to the ED with a diagnosis of ACS at day 30. RESULTS: Fifty-nine patients (48.7%) were diagnosed with ACS and 62 (51.3%) with nonspecific chest pain (NSCP). Median plasma sTREM-1 level at admission was significantly higher in the ACS group than the NSCP group and the control group (539.4 ± 330.3 pg/ml vs. 432.5 ± 196.4 pg/ml vs. 230.1 ± 85.5 pg/ml, respectively; P < 0.001) and positively correlated with the number of stenosed/occluded coronary arteries on angiography (P < 0.001). On logistic regression analysis, higher sTREM-1 levels predicted definite ACS vs. NSCP determined on day 30 (OR 1.29, 95% CI 1.07-1.54, P = 0.01) as well as with recurrent ACS (P = 0.04) and stroke (P = 0.02) at 6 months. CONCLUSIONS: Plasma sTREM-1 levels are significantly elevated in patients with ACS and might serve as a biomarker differentiating ACS from NSCP in the ED as well as an inflammatory biomarker for coronary artery disease severity and outcome.

[NEUROLOGIC COMPLICATIONS AROUND THE DIAGNOSIS OF KIKUCHI-FUJIMOTO DISEASE: A RARE PRESENTATION OF THE DISEASE OR A HINT OF AN ADDITIONAL DIAGNOSIS?]

INTRODUCTION: Neurologic symptoms are an extremely rare presentation of Kikuchi-Fujimoto disease. We report a case of a young female patient diagnosed with Kikuchi-Fujimoto disease, presenting with neurologic symptoms compatible with aseptic meningitis, along with radiographic findings which improved with steroidal treatment. Despite the rarity of these findings, they were reported as part of the disease manifestation, however, since Kikuchi-Fujimoto disease is associated with other diseases, such as systemic lupus erythematosus (SLE), other diagnoses cannot be ruled out.

The impact of tocilizumab on anxiety and depression in patients with rheumatoid arthritis.

BACKGROUND: Mood disorders, such as anxiety and depression, are extremely prevalent among patients with rheumatoid arthritis (RA). In this study, we assessed the impact of treatment with tocilizumab (TCZ), an IL-6 antagonist, upon anxiety and depressive symptoms in a cohort of RA patients. MATERIALS AND METHODS: Study participants were adults diagnosed with RA who received a weekly subcutaneous injection of tocilizumab for 24 weeks. We used the Hamilton Depression (HDRS) and Anxiety (HAMA) scores in order to assess the severity of depression and anxiety, respectively. RA disease activity indices and depression and anxiety levels were assessed at baseline, 4 weeks and study completion. RESULTS: Ultimately, 91 patients were included in the study. The mean age was 54 years, and the majority were female (79%). The mean score in all disease activity indices as well as depression and anxiety levels decreased dramatically from baseline to study completion. Sixty patients (66%) demonstrated a significant decrease in anxiety and/or depression levels. When logistic regression was performed, an HDRS score indicative of depression at study baseline demonstrated an independent association with a significant psychiatric response whilst older age and increased baseline weight were negatively associated. HAMA and HDRA scores correlated with the following RA disease activity parameters, respectively; HAQ-DI (r = .4, .42), DAS28 (r = .29, .32) and CDAI (0.28 and 0.33), all of them were statistically significant (P < .01). CONCLUSIONS: This study has demonstrated a favourable impact of TCZ therapy on parameters reflecting depression and anxiety severity in patients with RA.

A Cross-sectional Survey on the Preference of Patients with Rheumatoid Arthritis for Route of Administration of Disease-Modifying Anti-Rheumatic Drugs: Oral Target-Specific Versus Parenteral Biologic.

BACKGROUND: Guidelines recommend initiation of parenteral biologic or oral target-specific disease-modifying anti-rheumatic drugs (bDMARDs/tsDMARDs) in rheumatoid arthritis (RA) patients who do not adequately respond to conventional DMARDs. OBJECTIVES: To compare the preferred route of administration of bDMARDs or tsDMARDs in RA patients who were previously treated with at least one type. METHODS: A cross-sectional survey was conducted of consecutive RA patients previously prescribed bDMARDs or tsDMARDs. We analyzed the factors associated with patients' preferred route of administration. RESULTS: The cohort included 95 patients, mostly female (72.6%), seropositive (81.05%), mean age 63.4 ± 11.9 years. The oral route was preferred by 39 patients (41%) and 56 (59%) preferred the parenteral route. Most patients (65.9%) preferred to continue with their current route (P < 0.001). Switching from a current route was less common with patients who were currently using the oral route (13.3% vs. 38.2%, P = 0.04). Many patients (53.8%) who preferred the oral route had never experienced it before, while this was rare (3.6%) regarding the parenteral route (P = 0.0001). Employment status was associated with preference of the subcutaneous route over the intravenous route of bDMARDs (P = 0.01). Of the 21 patients who had previously experienced both parenteral and oral treatment, 16 (76.2%) preferred the oral route. CONCLUSIONS: RA patients preferred to continue treatment with an administration route they have already experienced. However, when choosing an unexperienced route, significantly more patients preferred the oral route. Our results strengthen the understanding of patient preferences, which could improve drug adherence, compliance, and disease outcome.

A Study of the Efficacy and Safety of Subcutaneous Injections of Tocilizumab in Adults with Rheumatoid Arthritis.

BACKGROUND: Tocilizumab is an interleukin 6 (IL-6) receptor antagonist used treat moderate to severe active rheumatoid arthritis (RA). Both intravenous (IV) and subcutaneous (SC) routes are approved for the treatment of adults with RA. OBJECTIVES: To evaluate SC tocilizumab in a real-life clinical setting. METHODS: Our study was a multi-center, open-label, single-arm study. Participants were adults with a diagnosis of active RA, previously treated with disease-modifying antirheumatic drugs (DMARDs), with or without biologic agents. Participants received a weekly SC injection of tocilizumab 162 mg as monotherapy or in combination with methotrexate or DMARDs for 24 weeks. Efficacy, safety, and immunogenicity were assessed. RESULTS: Treatment of 100 patients over 24 weeks resulted in improvement in all efficacy parameters assessed: Clinical Disease Activity Index, Disease Activity Score using 28 joint counts and erythrocyte sedimentation rate, American College of Rheumatology response scores, Simplified Disease Activity Index, tender and swollen joint counts, and patient-reported outcomes including fatigue, global assessment of disease activity, pain, and Health Assessment Quality of Life Disease Index. Improvement was achieved as early as the second week of treatment. There were 473 adverse events (AEs)/100 patient-years (PY) and 16.66 serious AEs/100 PY. The most common AEs were neutropenia (12%), leukopenia (11%), and increased hepatic enzymes (11%). Of a total of 42 PY, the rates of serious infections and AEs leading to discontinuation were 4.8, and 11.9 events/100 PY, respectively. CONCLUSIONS: The safety, tolerability, and efficacy profile of tocilizumab SC were comparable to those reported in other studies evaluating the IV and SC routes of administration.

Effect of Tocilizumab on Fatigue and Bone Mineral Density in Patients with Rheumatoid Arthritis.

BACKGROUND: Chronic fatigue is common among patients with rheumatoid arthritis (RA), affecting quality of life. Osteoporosis is a prevalent co-morbidity in RA patients. OBJECTIVES: To assess the effect of long-term treatment with tocilizumab on fatigue and bone mineral density (BMD) in RA patients with inadequate response to synthetic or biologic disease-modifying anti-rheumatic drugs. METHODS: In this multicenter, open-label, non-controlled, single-arm study, patients ≥ 18 years of age received intravenous tocilizumab 8 mg/kg every 4 weeks for 96 weeks. The primary outcome was the change in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue score from baseline to weeks 24, 48, 72, and 96. BMD was assessed before and 96 weeks after treatment. RESULTS: The study comprised 145 patients (mean age 53.4 ± 13.4 years, 83.4% women). Of these, 88 (60.7%) completed the 2 year treatment period. The mean FACIT-Fatigue score improved consistently starting from week 4 and showed a statistically significant increase of 5.0 ± 9.7, 6.8 ± 10.5, 7.3 ± 10.9, and 7.3 ± 10.4 from baseline to weeks 24, 48, 72, and 96, respectively (P < 0.0001). Mean BMD of femoral neck and total spine remained stable. Disease activity, acute phase reactants, and composite efficacy measures decreased during the study, while hemoglobin levels increased. Adverse events and serious adverse events were as expected for the known and previously described data. CONCLUSIONS: Tocilizumab therapy for 2 years significantly and clinically decreased fatigue. BMD remained stable and no new safety issue was reported.

Corneal melting in rheumatoid arthritis patients treated with a tectonic reinforcing corneolimbal graft: an interventional case series.

PURPOSE: Corneal melting with perforation is a severe ophthalmic complication of autoimmune disorders such as rheumatoid arthritis. It requires urgent medical management in order to maintain the integrity of the globe and preserve vision. Treating this complication by penetrating keratoplasty is problematic due to the high rate of recurrence of corneal melting as well as other complications. We describe the use of a tectonic fresh-tissue corneolimbal covering graft. METHODS: An interventional case series including three patients that presented to our tertiary center between 2000 and 2015 with corneal melting and perforation, secondary to rheumatoid arthritis. Emergency surgery included suturing of a 13.00- to 13.50-mm full-thickness fresh-tissue corneolimbal covering graft to the patient's posterior limbal zone. RESULTS: The corneolimbal graft maintained the integrity of the cornea in all cases, by sealing the perforation and promoting the creation of a fibrovascular scar at the area of corneal melting. There were no complications, recurrences of host corneal melting, or perforation during the follow-up period. CONCLUSION: Fresh-tissue full-thickness corneolimbal grafts may be used to cover emergency corneal melting and perforations secondary to rheumatoid arthritis.

[IgG4-RELATED DISEASE].

INTRODUCTION: IgG4-related disease is a syndrome of unknown etiology, which can affect any organ. It is characterized by lymphoplasmacytic infiltration of the affected organs that is rich in IgG4-positive plasma cells, fibrosis, and sometimes increased blood levels of IgG4. Treatment is determined according to the organs involved and the severity of involvement. Corticosteroids are considered to be the first line of treatment. In steroid-resistant or recurrent disease, immunosuppressive drugs or rituximab are used, although their efficacy has not been proven in clinical trials. This review describes the current understanding of the pathogenesis, clinical features, diagnosis and treatment of IgG4-related disease.

Elevated C-Reactive Protein Level Predicts Earlier Treatment with Tumor Necrosis Factor-Alpha Inhibitors in Psoriatic Arthritis.

BACKGROUND: Tumor necrosis factor-alpha (TNFα) inhibitors are indicated for patients with psoriatic arthritis (PsA) in whom conventional disease-modifying anti-rheumatic drugs (DMARDs) are insufficient to achieve disease remission. OBJECTIVES: To determine the value of acute-phase reactant levels at diagnosis of psoriatic arthritis in predicting the need for biologic treatment with TNFα inhibitors. METHODS: We conducted a longitudinal observational study of an inception cohort of 71 consecutive patients diagnosed with psoriatic arthritis. C-reactive protein (CRP) was assayed for all patients at their first visit. RESULTS: All patients were treated with one or more DMARDs, mainly methotrexate (81.6%). Thirty-seven patients (52.11%) had an inadequate response and received at least one TNF inhibitor. CRP level at diagnosis was positively correlated with need for a TNF inhibitor (P = 0.009, HR 1.8, 95% CI 1.27-1.85). Patients with CRP > 0.9 mg/dl at diagnosis started biologic treatment significantly earlier than patients with a lower level (P = 0.003, HR 2.62, 95% CI 0.393-2.5). CONCLUSIONS: In patients with psoriatic arthritis, CRP ≥ 0.9 mg/dl at diagnosis significantly predicts an earlier need for a TNF inhibitor to achieve disease control.

Guanine polynucleotides are self-antigens for human natural autoantibodies and are significantly reduced in the human genome.

In the course of investigating anti-DNA autoantibodies, we examined IgM and IgG antibodies to poly-G and other oligonucleotides in the sera of healthy persons and those diagnosed with systemic lupus erythematosus (SLE), scleroderma (SSc), or pemphigus vulgaris (PV); we used an antigen microarray and informatic analysis. We now report that all of the 135 humans studied, irrespective of health or autoimmune disease, manifested relatively high amounts of IgG antibodies binding to the 20-mer G oligonucleotide (G20); no participants entirely lacked this reactivity. IgG antibodies to homo-nucleotides A20, C20 or T20 were present only in the sera of SLE patients who were positive for antibodies to dsDNA. The prevalence of anti-G20 antibodies led us to survey human, mouse and Drosophila melanogaster (fruit fly) genomes for runs of T20 and G20 or more: runs of T20 appear > 170,000 times compared with only 93 runs of G20 or more in the human genome; of these runs, 40 were close to brain-associated genes. Mouse and fruit fly genomes showed significantly lower T20/G20 ratios than did human genomes. Moreover, sera from both healthy and SLE mice contained relatively little or no anti-G20 antibodies; so natural anti-G20 antibodies appear to be characteristic of humans. These unexpected observations invite investigation of the immune functions of anti-G20 antibodies in human health and disease and of runs of G20 in the human genome.

Soluble triggering receptor expressed on myeloid cells-1 is a biomarker of anti-CCP-positive, early rheumatoid arthritis.

OBJECTIVES: To assess serum soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) levels in disease-modifying antirheumatic drug (DMARD)-naïve early rheumatoid arthritis (ERA), to investigate the association of sTREM-1 levels with Disease Activity Score in 28 joints (DAS28) and seropositivity for anti-cyclic citrullinated peptide (CCP) antibody and to determine the predictive value of sTREM-1 with respect to clinical response to DMARD therapy. METHODS: Twenty-two consecutive patients with DMARD-naïve ERA were prospectively evaluated for serum sTREM-1 by means of ELISA at diagnosis and at the following clinic visit after prednisone and/or DMARD has been administered, and related to DAS28 and serum level of anti-CCP antibody. We compared the sTREM-1 level to that of 31 patients with established RA as well as to 24 controls. RESULTS: Serum sTREM-1 level was significantly higher in the DMARD-naïve ERA group (212.9 ± 388.9 ρg/mL) compared to established RA group (1478.0 ± 280.0 ρg/mL, P = 0.001) and normal control (34.4 ± 7.4 ρg/mL, P < 0.001). In the ERA group, elevated basal sTREM-1 level correlated with higher DAS28-CRP score (P = 0.001, HR 3.23, 95% CI 1.4-8.12), DAS28-ESR (P = 0.04, HR 2.34 95% CI 0.1-8.12), as well as predicted higher DAS28 score at the following encounter after DMARD treatment was administered (P = 0.001, HR 3.2 95% CI 1.1-7.2). Higher serum level of sTREM-1 correlated with higher titres of anti-CCP antibody (P < 0.001). CONCLUSIONS: Our results suggest that serum sTREM-1 may provide a novel biomarker for DMARD-naïve ERA as well as for seropositivity for anti-CCP antibody and RA activity.

Pemphigus vulgaris is characterized by low IgG reactivities to specific self-antigens along with high IgG reactivity to desmoglein 3.

Pemphigus vulgaris (PV) is an autoimmune skin disease, which has been characterized by IgG autoantibodies to desmoglein 3. Here we studied the antibody signatures of PV patients compared with healthy subjects and with patients with two other autoimmune diseases with skin manifestations (systemic lupus erythematosus and scleroderma), using an antigen microarray and informatics analysis. We now report a previously unobserved phenomenon--patients with PV, compared with the healthy subjects and the two other diseases, show a significant decrease in IgG autoantibodies to a specific set of self-antigens. This novel finding demonstrates that an autoimmune disease may be associated with a loss of specific, healthy IgG autoantibodies and not only with a gain of specific, pathogenic IgG autoantibodies.