SummarySystemic lupus erythematosus (SLE) is an autoimmune disease that can attack many different body organs; the triggering event is unknown. SLE has been associated with more than 100 different autoantibody reactivities -anti-dsDNA is prominent. Nevertheless, autoantibodies to dsDNA occur in only two-thirds of SLE patients. We previously reported the use of an antigen microarray to characterize SLE serology. We now report the results of an expanded study of serology in SLE patients and scleroderma (SSc) patients compared with healthy controls. The analysis validated and extended previous findings: two-thirds of SLE patients reacted to a large spectrum of self-molecules that overlapped with their reactivity to dsDNA; moreover, some SLE patients manifested a deficiency of natural IgM autoantibodies. Most significant was the finding that many SLE patients who were negative for autoantibodies to dsDNA manifested abnormal antibody responses to Epstein-Barr virus (EBV): these subjects made IgG antibodies to EBV antigens to which healthy subjects did not respond or they failed to make antibodies to EBV antigens to which healthy subjects did respond. This observation suggests that SLE may be associated with a defective immune response to EBV. The SSc patients shared many of these serological abnormalities with SLE patients, but differed from them in increased IgG autoantibodies to topoisomerase and centromere B; 84% of SLE patients and 58% of SSc patients could be detected by their abnormal antibodies to EBV. Hence an aberrant immune response to a ubiquitous viral infection such as EBV might set the stage for an autoimmune disease.

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.

The objective is to investigate the accrual rate and risk factors of chronic kidney disease (CKD) in an inception cohort of patients with systemic lupus erythematosus (SLE) followed at a single tertiary center. A prospectively collected database of 256 consecutive patients with SLE followed over a 25-year period was systematically interrogated for demographic, disease manifestations, co-morbidities, and outcome. Standardized SLE activity and damage scores were determined for the first and last study visits, and estimated glomerular filtration rate (eGFR; MDRD formula) was calculated at the time of diagnosis and at each year of the follow-up. CKD was defined as eGFR <60 ml/min/1.73 m(2). Results were analyzed with univariate and multivariate models and Kaplan-Meier curves, as appropriate. The cohort was predominantly female (90 %) and Jewish (91.1 %). Mean age at diagnosis was 38 ± 15.5 years, mean SLE activity score 6.4 ± 3.8, mean disease duration 8.8 ± 6.6 years, and mean damage score 0.2 ± 0.6. Seventy-five patients (30.8 %) were diagnosed with American College of Rheumatology (ACR)-defined lupus renal disease during the study period. There was a progressive decrease in eGFR over time. The prevalence of CKD was 46.7 % in patients with ACR-defined renal lupus disease and 16.4 % in those without. The hazards ratio for CKD was significantly higher in patients with lupus nephritis (LN) than without (p < 0.001). Earlier CKD was positively associated with hypertension (p = 0.01), older age at diagnosis (p = 0.01), and LN (p < 0.001), and negatively associated with hydroxychloroquine treatment (p < 0.001). The prevalence of CKD increases cumulatively in patients with SLE, also in those without overt lupus renal disease. Lupus renal disease poses a significant hazard for earlier development of CKD, and hypertension is a major risk factor for patients with and without nephritis. Antimalarial treatment is associated with renal preservation only in patients with lupus nephritis.

We sought to determine serum triggering receptor expressed on myeloid cell-1 (sTREM-1) level in a cohort of patients with systemic lupus erythematosus (SLE). Serum sTREM-1 level of 98 patients with SLE and 49 healthy controls was assayed by ELISA. Serum sTREM-1 level was significantly elevated in a cohort of 78 unselected consecutively recruited patients with SLE (mean 1.1 ± 2.8 ρg/ml, median 0.02 ρg/ml) compared to that of the controls (mean 0.11 ± 0.3 ρg/ml, median 0 ρg/ml; p < 0.0001). We also determined serum sTREM-1 level of 20 SLE patients with a concurrent infection (mean 0.6 ± 1.1 ρg/ml, median 0.12 ρg/ml) and found it not statistically significant compared with that of the patients without infection. Serum sTREM-1 level did not correlate with SLE disease activity. Our finding of elevated serum sTREM-1 level suggests an increased shedding of TREM-1 in SLE and a possible novel pathway of innate immune response in autoimmunity.