Faculty Bibliography

OBJECTIVE: Anti-C1q has been associated with systemic lupus erythematosus (SLE) and lupus nephritis in previous studies. We studied anti-C1q specificity for SLE (vs rheumatic disease controls) and the association with SLE manifestations in an international multicenter study. METHODS: Information and blood samples were obtained in a cross-sectional study from patients with SLE (n = 308) and other rheumatologic diseases (n = 389) from 25 clinical sites (84% female, 68% Caucasian, 17% African descent, 8% Asian, 7% other). IgG anti-C1q against the collagen-like region was measured by ELISA. RESULTS: Prevalence of anti-C1q was 28% (86/308) in patients with SLE and 13% (49/389) in controls (OR = 2.7, 95% CI: 1.8-4, p < 0.001). Anti-C1q was associated with proteinuria (OR = 3.0, 95% CI: 1.7-5.1, p < 0.001), red cell casts (OR = 2.6, 95% CI: 1.2-5.4, p = 0.015), anti-dsDNA (OR = 3.4, 95% CI: 1.9-6.1, p < 0.001) and anti-Smith (OR = 2.8, 95% CI: 1.5-5.0, p = 0.01). Anti-C1q was independently associated with renal involvement after adjustment for demographics, ANA, anti-dsDNA and low complement (OR = 2.3, 95% CI: 1.3-4.2, p < 0.01). Simultaneously positive anti-C1q, anti-dsDNA and low complement was strongly associated with renal involvement (OR = 14.9, 95% CI: 5.8-38.4, p < 0.01). CONCLUSIONS: Anti-C1q was more common in patients with SLE and those of Asian race/ethnicity. We confirmed a significant association of anti-C1q with renal involvement, independent of demographics and other serologies. Anti-C1q in combination with anti-dsDNA and low complement was the strongest serological association with renal involvement. These data support the usefulness of anti-C1q in SLE, especially in lupus nephritis.

Objective: To estimate the early prevalence of various electrocardiographic (ECG) abnormalities in patients with SLE and to evaluate possible associations between repolarization changes (increased corrected QT, QTc, and QT dispersion, QTd) and clinical and laboratory variables, including the anti-Ro/SSA level and specificity (52 or 60KDa). Methods: We studied adult SLE patients from 19 centers participating in the Systemic Lupus International Collaborating Clinics (SLICC) Inception Registry. Demographics, disease activity (SLEDAI-2K), disease damage (SLICC/ACR DI), and laboratory data from the baseline or first follow-up visit were assessed. Multivariate logistic and linear regression models were used to asses for any cross-sectional associations between anti-Ro/SSA and ECG repolarization abnormalities. Results: For the 779 patients included, mean age (SD) was 35.6 years (13.8), 88.4% were women, and mean disease duration was 10.5 months (14.4). Mean SLEDAI-2K was 5.4 (5.6) and mean SLICC/ACR DI was 0.5 (1.0). ECG abnormalities were frequent and included non-specific ST-T changes (30.9%), possible left ventricular hypertrophy (5.4%) and supraventricular arrhythmias (1.3%). A QTc >/= 440ms was found in 15.3%, while QTc >/= 460ms was found in 5.3%. Mean (SD) QTd was 34.2ms (14.7) and QTd >/= 40ms was frequent (38.1%). Neither the specificity, nor the level of anti-Ro/SSA was associated with QTc duration or QTd, although confidence intervals were wide. Total DI was significantly associated with a QTc interval exceeding 440 ms (OR 1.38 95% CI 1.06, 1.79). Conclusion: A substantial proportion of recent-onset SLE patients exhibit repolarization abnormalities although severe abnormalities were rare. (c) 2014 American College of Rheumatology.

This review describes eight 'great ideas' regarding bench-to-bedside considerations in systemic lupus erythematosus (SLE) presented at the second international LUPUS meeting in Quebec, September 2014. The topics included: correcting the impaired clearance of apoptotic fragments; optimisation of clinical trial design: the PERFECT (Pre Evaluation Reducing Frighteningly Elevated Coverable Targets) study; lipidomics and metabolomics in SLE; importance of the inflammasome; identification and treatment of asymptomatic autoimmunity: prevention of SLE; combining low doses of hydroxychloroquine and quinacrine for long-term maintenance therapy of SLE; reducing emergency room visits and the critical relevance of the autoantigen.

Approximately 40% of patients who survive acute episodes of thrombotic thrombocytopenic purpura (TTP) associated with severe acquired ADAMTS13 deficiency experience one or more relapses. Risk factors for relapse other than severe ADAMTS13 deficiency and ADAMTS13 autoantibodies are unknown. ADAMTS13 autoantibodies, TTP episodes following infection or type I interferon treatment and reported ensuing systemic lupus erythematosus in some patients suggest immune dysregulation. This cross-sectional study asked whether autoantibodies against RNA-binding proteins or peripheral blood gene expression profiles measured during remission are associated with history of prior relapse in acquired ADAMTS13-deficient TTP. Peripheral blood from 38 well-characterized patients with autoimmune ADAMTS13-deficient TTP in remission was examined for autoantibodies and global gene expression. A subset of TTP patients (9 patients, 24%) exhibited a peripheral blood gene signature composed of elevated ribosomal transcripts that associated with prior relapse. A non-overlapping subset of TTP patients (9 patients, 24%) displayed a peripheral blood type I interferon gene signature that associated with autoantibodies to RNA-binding proteins but not with history of relapse. Patients who had relapsed bimodally expressed higher HLA transcript levels independently of ribosomal transcripts. Presence of any one potential risk factor (ribosomal gene signature, elevated HLA-DRB1, elevated HLA-DRB5) associated with relapse (OR = 38.4; p = 0.0002) more closely than any factor alone or all factors together. Levels of immune transcripts typical of natural killer (NK) and T lymphocytes positively correlated with ribosomal gene expression and number of prior episodes but not with time since the most recent episode. Flow cytometry confirmed elevated expression of cell surface markers encoded by these transcripts on T and/or NK cell subsets of patients who had relapsed. These data associate elevated ribosomal and immune transcripts with relapse history in acquired, ADAMTS13-deficient TTP.