Hypothesis: interleukin-5 production impairment can be a key point in the pathogenesis of the MHC-linked selective IgA deficiency.
Selective IgA deficiency (IgA-D) is associated with the expression of some human leukocyte antigens (HLA) haplotypes and Major Hystocompatibility Complex (MHC) gene products have been suggested to be involved in the regulation of IgA synthesis. Recently, we have obtained evidences indicating that MHC influences the production of IgA and interleukin-5 (IL-5) both in humans and in mice. Lymphnode cells from pychril chloride (PC1) immunised BALB/c mice (bearing the H-2d haplotype) fail to produce IL-5 when stimulated in vitro with PC1 and this correlates with low antigen specific IgA production in vivo. In contrast using congenic BALB/k mice (bearing the H-2k haplotype) an high production both of IL-5 and of PC1-specific IgA is observed. Moreover, in vivo or in vitro administration of IL-5 to BALB/c mice was able to increase the production of antigen specific IgA. Similar evidences have been obtained by evaluation of the HLA influence on circulating immunoglobulin levels and interleukin production in normal HLA typed subjects. In fact HLA-B8, DR3 positive subjects show reduced level of serum IgA and their peripheral blood mononuclear cells stimulated with mitogen produce significantly reduced amounts of IL-5, IL-12, IL-2 and Interferon-gamma. We hypothesise that HLA-B8, DR3 associated IgA deficiency, known to be asymptomatic, can be due to a lack of subsequent signals, in particular of IL-5, involved in the late regulation of B cell differentiation. Preliminary evidences demonstrating that low amounts of human recombinant IL-5 are able to reconstitute IgA production by cells from HLA-B8, DR3 IgA-D subjects, seem to confirm this hypothesis.
Lio
D
D
General Pathology Institute, Palermo, Italy.
D'Anna
C
C
Leone
F
F
Currò
M F
MF
Candore
G
G
Caruso
C
C
D000818:Animals; D008040:Genetic Linkage; D015795:HLA-B8 Antigen; D015803:HLA-DR3 Antigen; D006801:Humans; D017098:IgA Deficiency / Q000209:etiology* / Q000235:genetics / Q000276:immunology*; D007070:Immunoglobulin A / Q000096:biosynthesis; D066298:In Vitro Techniques; D015848:Interleukin-5 / Q000096:biosynthesis* / Q000494:pharmacology; D008285:Major Histocompatibility Complex; D051379:Mice; D008807:Mice, Inbred BALB C; D008954:Models, Biological; D011994:Recombinant Proteins / Q000494:pharmacology
D015795:HLA-B8 Antigen; D015803:HLA-DR3 Antigen; D007070:Immunoglobulin A; D015848:Interleukin-5; D011994:Recombinant Proteins