CD4-positive cells from patients with IgA nephropathy demonstrate increased mRNA of cytokines that induce the IgA switch and differentiation

J Pathol. 1994 Sep;174(1):13-22. doi: 10.1002/path.1711740104.

Abstract

IgA nephropathy (IgAN) is characterized by raised serum IgA1 and mesangial IgA1 deposits. We have previously shown increased T-cell activation in IgAN. Recently, transforming growth factor-beta (TGF-beta) has been shown to induce IgA isotype switch at a clonal level and interleukin 5 (IL5) promotes differentiation into IgA-bearing B cells. In the present study we have examined the TGF-beta and IL5 mRNA expression by mitogen-activated CD4-positive T cells from patients with IgAN (n = 25), patients with other primary nephritides (CGN) (n = 24), and healthy control subjects (n = 25). The cytokine genes were analysed by reverse transcription (RT)-polymerase chain reaction (PCR) and were semi-quantitated by normalizing the differences occurring during RT and PCR using a housekeeping gene, beta-actin. CD4-positive T cells from IgA nephritic patients expressed a higher level of IL5 mRNA than healthy controls (P < 0.01) and patients with CGN (P < 0.005). CD4-positive T cells from IgA nephritic patients expressed a higher level of TGF-beta mRNA than healthy controls (P < 0.01) but no difference was demonstrated on comparison with CGN patients. Elevated TGF-beta mRNA expression in patients with CGN probably reflects its other important function as a 'sclerogenic' factor involved in the glomerulosclerosis found in these nephritides. Our data suggest that there is increased expression of cytokine genes which induce the IgA isotype switch and differentiation; these immunological abnormalities may be important in the pathogenesis of IgAN.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Base Sequence
  • CD4-Positive T-Lymphocytes / immunology*
  • Cytokines / genetics*
  • Female
  • Gene Expression
  • Glomerulonephritis, IGA / genetics
  • Glomerulonephritis, IGA / immunology*
  • Humans
  • Immunoglobulin A / biosynthesis*
  • Immunoglobulin A / blood
  • Interleukin-5 / genetics
  • Male
  • Middle Aged
  • Molecular Sequence Data
  • Polymerase Chain Reaction / methods
  • RNA, Messenger / genetics*
  • Transforming Growth Factor beta / genetics

Substances

  • Cytokines
  • Immunoglobulin A
  • Interleukin-5
  • RNA, Messenger
  • Transforming Growth Factor beta