Background: Neuromyelitis optica (NMO) is often associated with other clinical or serological markers of non-organ-specific autoimmunity. Objective: ToevaluatetherelationshipbetweenNMOspectrum disorders (NMOSDs), including NMO, longitudinally extensive transverse myelitis, and recurrent optic neuritis, and autoimmune disease. We concentrated on the association with systemic lupus erythematosus (SLE), Sjögren syndrome (SS), or serological evidence of these disorders, which commonly is a source of diagnostic confusion.

Systemic lupus erythematosus (SLE), a connective tissue disease characterized by the production of autoantibodies, can affect all organ systems. Cardiac involvement in patients with SLE has been described since the early 20th century. The manifestations are numerous and can involve all components of the heart, including the pericardium, conduction system, myocardium, valves, and coronary arteries. In recent years, echocardiography has yielded additional information about the heart in patients who have SLE with and without clinical cardiac involvement. Moreover, antiphospholipid antibodies have been linked to several cardiac manifestations in patients with SLE, including valvular abnormalities and possibly coronary artery disease. This updated, comprehensive review summarizes the new literature on SLE and the heart.

Objective To estimate the annual incidence and prevalence of and frequency of mortality associated with antiphospholipid syndrome (APS). Methods An inception cohort of patients with incident APS in 2000–2015 from a geographically well‐defined population was identified based on comprehensive individual medical records review. All cases met the 2006 Sydney criteria for APS (primary definition) or had a diagnosis of APS confirmed by physician consensus (secondary definition). Levels of lupus anticoagulant, IgM and IgG anticardiolipin antibodies, and anti–β2‐glycoprotein I antibodies were tested in a centralized laboratory. Incidence rates were age‐ and sex‐adjusted to the 2010 US white population. Prevalence estimates were obtained from the incidence rates, assuming that there was no increased mortality associated with APS and that migration in or out of the area was independent of disease status. Results Among this cohort in 2000–2015, 33 cases of incident APS, as defined by the Sydney criteria, were identified (mean age of patients 54.2 years; 55% female, 97% white). The annual incidence of APS in adults ages ≥18 years was 2.1 (95% confidence interval [95% CI] 1.4–2.8) per 100,000 population. Incidence rates were similar in both sexes. The estimated prevalence of APS was 50 (95% CI 42–58) per 100,000 population, and was similar in both sexes. Six patients (18%) had a concurrent diagnosis of systemic lupus erythematosus. The most frequent clinical manifestation was deep vein thrombosis. The overall frequency of mortality among patients with APS was not significantly different from that in the general population (standardized mortality ratio 1.61, 95% CI 0.74–3.05). Conclusion APS occurred in ~2 persons per 100,000 population per year. The estimated prevalence was 50 per 100,000 population. Overall mortality was not notably different from that observed in the general population.

Complications of portal hypertension, cirrhosis, and hepatic encephalopathy are rare manifestations of SLE unless coexistent liver disease such as NAFLD, viral hepatitis, or AIH is present.

PURPOSE The objective of this study was to determine the impact of lupus nephritis disease activity on maternal and fetal outcomes in pregnant patients with systemic lupus erythematosus (SLE). METHODS Medical records of all pregnant patients with SLE treated at our institution between 1976 and 2007 were reviewed. All patients met American College of Rheumatology classification criteria for SLE. Demographic data, history of lupus nephritis, nephritis disease activity, and maternal and fetal outcomes of pregnancy were abstracted. Active lupus nephritis was defined as the presence of proteinuria > 0.5 g/day and/or active urinary sediment with or without an elevation in serum creatinine (Cr). Quiescent lupus nephritis was confirmed in the presence of proteinuria < 0.5 mg/day and inactive urinary sediment. RESULTS We identified fifty-eight patients with ninety pregnancies. Compared to pregnancies in SLE patients without renal involvement (n=47), pregnancies in patients with active lupus nephritis (n=23) were associated with a higher incidence of maternal complications (57% vs. 11%, p<0.001), whereas those with quiescent lupus nephritis (n=20) were not (35% vs. 11%, p=0.10). Women with active lupus nephritis were more likely to deliver preterm than women without lupus nephritis, median of 34 weeks vs. 40 gestational weeks, respectively (p=0.002), and were more likely to suffer fetal loss (35% vs 9%, p=0.031). CONCLUSION Active, but not quiescent, lupus nephritis during pregnancy is associated with a higher incidence of maternal and fetal complications compared to pregnancies in SLE patients without renal involvement.

Objectives To characterize the epidemiology of mixed connective tissue disease (MCTD) from 1983 to 2014. Methods An inception cohort of patients with incident MCTD in 1985-2014 in Olmsted County, Minnesota was identified based on comprehensive individual medical record review. Diagnosis of MCTD required fulfillment of at least one of the four widely-accepted diagnostic criteria without fulfillment of classification criteria for other connective tissue diseases. Data were collected on demographic characteristics, clinical presentation, laboratory investigations and mortality. Results A total of 50 incident cases of MCTD were identified (mean age 48.1 years and 84% were female). The annual incidence of MCTD was 1.9 per 100,000 population. Raynaud's phenomenon was the most common initial symptoms (50%) followed by arthralgia (30%) and swollen hands (16%). The diagnosis was frequently delayed with the median time from first symptom to fulfillment of criteria of 3.6 years. At fulfillment of criteria, arthralgia was the most prevalent manifestation (86%) followed by Raynaud's phenomenon (80%), swollen hands (64%), leukopenia/lymphopenia (44%) and heartburn (38%). Evolution to other connective tissue occurred infrequently with 10-year rate of evolution of 8.5% and 6.3% for SLE and SSc, respectively. The overall mortality was not different form the general population with standardized mortality ratio: 1.1 (95% CI, 0.4-2.6). Conclusions This study was the first population-based study of MCTD to provide a complete picture of epidemiology and clinical characteristics of MCTD. MCTD occurred in about 2 persons per 100,000 per year. Evolution to other connective diseases occurred infrequently and the mortality was not affected.

A pathogenic hallmark of rheumatoid arthritis (RA) is persistent activation of self-reactive CD4 + T cells. The cause of this aberrant activity remains elusive. We report here detection of autoantibodies against B7-H1, a recently described member of the B7 family, in 29% of patients with RA versus 4% of healthy donors. High-level expression of cell surface B7-H1 are found on activated human CD4 + , CD8 + , and CD45RO + T cells. Immobilized autoantibodies to B7-H1 are capable of costimulating the proliferation of CD4 + T cells in vitro, and the presence of these autoantibodies correlates with active disease status. Using immobilized B7-H1 mAb's and programmed death 1Ig, we demonstrate that engagement of B7-H1 on CD4 + T cells costimulates proliferation and secretion of IL-10, and subsequently leads to programmed cell death, accompanied with upregulated expression of TNF-related apoptosis-inducing ligand and activation of caspase-3. Taken together with our previous findings, these data indicate a bidirectional signaling role of B7-H1 in T cell costimulation and apoptosis and implicate B7-H1 autoantibodies as contributing to the progression of RA by inducing aberrant T cell responses.

A pathogenic hallmark of rheumatoid arthritis (RA) is persistent activation of self-reactive CD4 + T cells. The cause of this aberrant activity remains elusive. We report here detection of autoantibodies against B7-H1, a recently described member of the B7 family, in 29% of patients with RA versus 4% of healthy donors. High-level expression of cell surface B7-H1 are found on activated human CD4 + , CD8 + , and CD45RO + T cells. Immobilized autoantibodies to B7-H1 are capable of costimulating the proliferation of CD4 + T cells in vitro, and the presence of these autoantibodies correlates with active disease status. Using immobilized B7-H1 mAb's and programmed death 1Ig, we demonstrate that engagement of B7-H1 on CD4 + T cells costimulates proliferation and secretion of IL-10, and subsequently leads to programmed cell death, accompanied with upregulated expression of TNF-related apoptosis-inducing ligand and activation of caspase-3. Taken together with our previous findings, these data indicate a bidirectional signaling role of B7-H1 in T cell costimulation and apoptosis and implicate B7-H1 autoantibodies as contributing to the progression of RA by inducing aberrant T cell responses.