MO314ANA POSITIVITY IN IGA NEPHROPATHY: IS SYSTEMIC LUPUS ERYTHEMATOSUS COMING UP?

Background and Aim. IgA nephropathy (IgAN) is the most common chronic primary glomerulonephritis leading to progressive renal failure in 1/3 of patients. Although it is a limited non-systemic renal disease, many systemic diseases, such as Systemic Lupus Erythematosus (SLE), are sporadically associated with mesangial IgA deposits. We investigate frequency and meaning of ANA positivity in IgAN. Methods. All biopsy-proven IgAN patients followed in our Unit with ANA positivity were selected. Data are compared by non parametric test (Wilcoxon signed-rank test). Results. 15/68 (22%) IgAN patients resulted ANA+ during a 9-year median follow-up. 10 were females and five were male. Mean age was low. Renal function was normal in 9/15. 24 h Proteinuria was non nephrotic in 15/16. In 10 patients there was low C3. Patient characteristics are summarized in Table 1. At follow-up, renal function did not change significantly (p=NS), however mean 24h-Uprot reduced (p=0.075) Table 2. One male developed SLE, one female a lupus-like Mixed Connective Tissue Disease. Conclusions. Our data suggest that 1) in 22% of IgAN patients ANA positivity could be detected; 2) ANA+ IgAN patients are mostly women with normal renal function and non nephrotic proteinuria; 3) after a median 9-year follow-up, ANA+ IgAN patients, on therapy, presented a stable renal function and a reduced proteinuria; 4) ANA+ IgAN patients could develop SLE. More clinical observations and studies are needed for supporting the hypothesis that IgAN+ANA positivity could be part of a new clinical entity of SLE patients.

Serum Levels of Joining Chain-Containing IgA1 Are Not Elevated in Patients with IgA Nephropathy

Background. It has been suggested that mesangial IgA deposits are dimeric or polymeric in IgA nephropathy (IgAN). However, evidence concerning the molecular form of serum IgA in IgAN is controversial. And there is no direct evidence that the serum levels of joining chain- (J chain-) containing IgA (J-IgA) are elevated in IgAN. In this study, we aimed to measure serum J-IgA and glomerular J chain deposition with anti-J chain monoclonal antibody in IgAN. Methods. BALB/c mice were immunized with human J chain-GST recombinant peptide to obtain anti-J chain monoclonal antibody. The levels of serum total IgA and J-IgA were measured by sandwich enzyme-linked immunosorbent assay in 115 patients with IgAN and 117 healthy volunteers. J chain deposition in kidney specimens was analyzed by immunohistochemistry staining. Results. Serum levels of total IgA1 were elevated in IgAN patients compared to healthy subjects. However, serum levels of IgA, J-IgA, and J chain-containing IgA1 (J-IgA1), the J-IgA to total IgA ratio, and the J-IgA1 to total IgA1 ratio were not significantly different between IgAN patients and healthy subjects. Western blot analysis and gel filtration analysis using purified IgA1 also showed that the proportion of J chain-containing polymeric IgA1 was lower in IgAN patients compared to healthy subjects. No correlation was found between serum J-IgA or J-IgA1 and clinical features in IgAN. Immunohistochemistry analysis showed that glomerular J chain was positive in 12 IgAN patients (57.1%). The values of the J-IgA to IgA ratio and J-IgA1 to IgA ratio were significantly higher in IgAN patients with glomerular J chain deposition than those without. However, the serum levels of J-IgA and J-IgA1 and the J-IgA1 to IgA1 ratio were not significantly higher in two subgroups. Conclusions. Although serum levels of total IgA1 were elevated in IgAN, the serum levels of J-IgA1 were not elevated. And serum J-IgA, serum J-IgA1, and J chain deposition were not correlated with disease severity in IgAN.

Back-Pack Mice as a Model of Renal Mesangial IgA Dimers Deposition

Mesangial IgA in IgA nephropathy are dimers with a J chain but no poly-Ig receptor. This molecular structure has led to the hypothesis that these IgA are issued from the lamina propria of mucosal areas, reaching the kidney by way of the peripheral blood. The availability of hybridomas producing IgA dimers provided an opportunity to test this hypothesis in a new experimental model of IgA nephropathy. Mice were injected subcutaneously (back-pack mice) or intraperitoneally with hybridoma cells secreting either monoclonal IgA dimers, or monoclonal IgA monomers. The influence of immune complex formation was also tested in both these models. Renal IgA deposition was investigated 12 days after the injection of hybridoma cells. Backpack mice developed highly vascularized subcutaneous tumors. Mesangial IgA deposits were observed only in dimeric IgA hybridoma back-pack animals. No significant staining was observed in glomeruli from animals injected with hybridoma cells producing monomeric IgA. None of the hybridomas induced mesangial deposition when injected intraperitoneally. This animal model demonstrates the capacity of circulating IgA dimers to spontaneously form mesangial deposits and contributes to confirm the involvement of abnormalities of mucosal immunity in the pathogenesis of IgA nephropathy.