ABSTRACT
OBJECTIVES: To determine prevalence and clinical associations of anti-FHL1 autoantibodies in patients with idiopathic inflammatory myopathies (IIM), and to evaluate autoantibody levels over time. METHODS: Sera at the time of diagnosis from patients with IIM (n = 449), autoimmune disease controls (DC, n = 130), neuromuscular diseases (NMD, n = 16) and healthy controls (HC, n = 100) were analyzed for anti-FHL1 autoantibodies by Enzyme-Linked ImmunoSorbent Assay (ELISA). Patients with IIM FHL1+ and FHL1- were included in a longitudinal analysis. Serum levels were correlated to disease activity. RESULTS: Autoantibodies to FHL1 were more frequent in patients with IIM (122/449, 27%) compared with DC (Autoimmune DC and NMD, 13/146, 9%, p< 0.001) and HC (3/100,3%, p< 0.001). Anti-FHL1 levels were higher in IIM [median (IQR)=0.62 (0.15-1.04)] in comparison with DC [0.22 (0.08-0.58)], HC [0.35 (0.23-0.47)] and NMD [0.48 (0.36-0.80)] p< 0.001. Anti-FHL1+ patients with IIM were younger at time of diagnosis compared with the anti-FHL1- group (p= 0.05) and were seronegative for other autoantibodies in 25%.In the first follow-up anti-FHL1+ sample 20/33 (60%) positive at baseline had turned negative for anti-FHL1 autoantibodies. Anti-FHL1 autoantibodies rarely appeared after initiating treatment. Anti-FHL1 autoantibody levels correlated with CK (r = 0.62, p= 0.01), disease activity measure MYOACT (n = 14, p= 0.004) and inversely with manual muscle test-8 (r=-0.59, p= 0.02) at baseline. CONCLUSIONS: Anti-FHL1 autoantibodies were present in 27% of patients with IIM, of these 25% were negative for other autoantibodies. Other autoimmune diseases had lower frequencies and levels. Anti-FHL1 levels often decreased with immunosuppressive treatment, correlated with disease activity measures at diagnosis and rarely appeared after start of treatment.
ABSTRACT
INTRODUCTION: The initiation and progression of diabetic nephropathy (DN) is complex. Quantification of mRNA expression in urinary sediment cells (USCs) has emerged as a novel strategy for studying kidney diseases. Insulin requires a family of insulin receptor substrate (IRS) proteins for its physiological effects, and many reports have highlighted the role of insulin and IRS proteins in kidney physiology and disease. This study aimed to assess IRS2 expression in USCs of patients with diabetes mellitus, DN, and nondiabetic chronic kidney disease. MATERIALS AND METHODS: To quantify IRS2 expression, RNA was extracted from USCs of 223 individuals comprised of diabetes mellitus, DN, and nondiabetic chronic kidney disease as well as a healthy control group. The cDNA was synthesized and comparative TaqMan real-time reverse transcript polymerase chain reaction was used in the presence of beta actin gene as a reference gene for normalization, relative to the control. RESULTS: Our data showed that the USCs expression of IRS2 gene was significantly increased in the DN patients compared with other groups (P < .001). The IRS2 expression was not significantly different between microalbuminuria and macroalbuminuria conditions or different stages of DN, except for the end-stage renal disease where the expression was lower. CONCLUSIONS: In patients with DN, urinary mRNA expression of the IRS2 gene is associated with kidney function. Our result suggests that serial measurement of urinary expression of this gene may have a value for early detection of kidney injury in diabetic patients.