Light-Chain Composition of Serum IgA1 and In Vitro IgA1 Production in IgA Nephropathy

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Abstract
A predominant expression of IgA1 in mesangial deposits, serum, and bone marrow culture supernatants has been shown in IgA nephropathy (IgAN). Furthermore an excess of λ light chains in both mesangial deposits and serum IgA has been observed. However, the origin of mesangial IgA remains controversial. In the present study, we have examined the IgA1 light chain type in IgAN. Total IgA1, IgA1K and IgAlλ were measured by ELISA in serum and culture supernatants from spontaneous and pokeweed-mitogen (PWM)- stimulated peripheral blood mononuclear cells (PBMC). We observed an increase in IgA and IgAl serum concentrations in IgA nephropathy patients, with a ratio of serum IgA1 to total serum IgA identical between patients and controls. The concentration of serum IgAk did not differ between patients and controls but patients had a significantly higher concentration of serum IgAλ. The IgA1K to IgA1λ ratio was 1.06 ± 0.42 in IgAN patients versus 1.55 ± 0.36 in controls (P<0.01). By contrast, the concentrations of IgA1K and IgA1λ in PBMC culture supernatants, both spontaneous and PWM-stimulated, were identical in patients and controls. Therefore, there is a specific increase in IgA1λ in patients' sera. This contrasts with the normal IgA1 production by PBMC, which are derived from mucosal-associated lymphoid tissues. This suggests that IgA isotypic deregulation is confined to the bone marrow compartment and is not a generalised defect of the IgA system.

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