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Abstract Most outcome studies of rheumatic diseases report outcomes ascertained on a single occasion. While single assessments are sufficient for terminal or irreversible outcomes, they may not be sufficiently informative if outcomes change or fluctuate over time. Consequently, longitudinal studies that measure non-terminal outcomes repeatedly afford a better understanding of disease evolution. Longitudinal studies require special analytic methods. Newer longitudinal analytic methods have evolved tremendously to deal with common challenges in longitudinal observational studies. In recent years, an increasing number of studies have used longitudinal design. This review aims to help readers understand and apply the findings from longitudinal studies. Using a cohort of children with juvenile dermatomyositis (JDM), we illustrate how to study evolution of disease activity in JDM using longitudinal methods.

Congenital heart block (CHB) is a transplacentally acquired autoimmune disease associated with anti-Ro/SSA and anti-La/SSB maternal autoantibodies and is characterized primarily by atrioventricular (AV) block of the fetal heart. This study aims to investigate whether the T-type calcium channel subunit α1G may be a fetal target of maternal sera autoantibodies in CHB.We demonstrate differential mRNA expression of the T-type calcium channel CACNA1G (α1G gene) in the AV junction of human fetal hearts compared to the apex (18-22.6 weeks gestation). Using human fetal hearts (20-22 wks gestation), our immunoprecipitation (IP), Western blot analysis and immunofluorescence (IF) staining results, taken together, demonstrate accessibility of the α1G epitope on the surfaces of cardiomyocytes as well as reactivity of maternal serum from CHB affected pregnancies to the α1G protein. By ELISA we demonstrated maternal sera reactivity to α1G was significantly higher in CHB maternal sera compared to controls, and reactivity was epitope mapped to a peptide designated as p305 (corresponding to aa305-319 of the extracellular loop linking transmembrane segments S5-S6 in α1G repeat I). Maternal sera from CHB affected pregnancies also reacted more weakly to the homologous region (7/15 amino acids conserved) of the α1H channel. Electrophysiology experiments with single-cell patch-clamp also demonstrated effects of CHB maternal sera on T-type current in mouse sinoatrial node (SAN) cells.Taken together, these results indicate that CHB maternal sera antibodies readily target an extracellular epitope of α1G T-type calcium channels in human fetal cardiomyocytes. CHB maternal sera also show reactivity for α1H suggesting that autoantibodies can target multiple fetal targets.

Lipid abnormalities in patients with systemic lupus erythematosus (SLE) are common and are likely to be one of the causes of premature atherosclerosis in these patients. This study was undertaken to serially examine the lipid profile in pediatric patients with SLE to determine the roles of active disease and therapy in altering lipid levels.Serial lipid measurements were obtained in an inception cohort of 139 pediatric patients with SLE at the time of treatment with either a constant dose or differing doses of prednisone, and annually. The levels of cholesterol, triglycerides, low‐density lipoprotein (LDL), and high‐density lipoprotein (HDL) were correlated with measures of disease activity and prednisone dose.At the time of SLE diagnosis in this pediatric cohort, the mean values for all lipids were abnormal. With each reduction in prednisone dose, there was a statistically significant decrease in cholesterol and triglyceride levels (P < 0.001) but not HDL or LDL levels. Nephrotic‐range proteinuria was associated with altered cholesterol, triglyceride, and LDL levels, whereas changes in HDL were more commonly associated with active nephritis. In the absence of nephrotic‐range proteinuria, increases in prednisone dose were associated with increased levels of all lipids, including HDL.Active SLE leads to a proatherogenic lipid profile. Levels of cholesterol and LDL were mainly associated with the dose of prednisone, and were abnormal only during very high disease activity. Triglyceride levels were mainly associated with proteinuria, while changes in HDL were associated with active SLE and a high dose of prednisone. Our results suggest that the lipid profile in pediatric SLE is the result of a complex interaction of disease manifestations and the effects of prednisone therapy. [ABSTRACT FROM AUTHOR]

Inflammatory central nervous system (CNS) diseases in childhood comprise a wide spectrum of heterogeneous conditions. We studied 4 children with primary CNS vasculitis in whom results of magnetic resonance imaging studies were abnormal but results of conventional angiography were normal. We determined that angiography‐negative, biopsy‐confirmed primary small‐vessel CNS vasculitis is a previously unrecognized distinct disease entity in children. The diagnosis must be considered in a child with a progressive, acquired diffuse or focal neurologic deficit, even if the results of conventional angiography are normal. A lesional brain biopsy is required to confirm the diagnosis. Use of immunosuppressive therapy plus aspirin leads to an excellent neurologic outcome. [ABSTRACT FROM AUTHOR]

Systemic lupus erythematosus (SLE) is an autoimmune disease with a strong ethnic and gender bias. In a transancestral genetic association study, Langefeldet al. identify 24 novel regions associated with risk to lupus and propose a cumulative hits hypothesis for loci conferring risk to SLE.