Brief report: immunoglobulin A deficiency in a subset of autistic subjects.

Abstract

We recently reported (Warren, Burger, Odell, Torres, & Warren, 1994) that a major subset of our autistic subjects has decreased plasma C4B levels resulting from inheritance of a null allele (no protein produced) of the C4B gene (Warren et al, 1991) located in the middle of the major histocompatibility complex (MHC) on chromosome 6. The C4B gene and the tightly linked structurally and functionally similar C4A gene encode products, designated as C4B and C4A proteins, that share several structural and functional characteristics identifying them as C4. However, they are distinct in other characteristics, most notably hemolytic activity; with C4B proteins having about four times more activity than C4A (Isenman & Young, 1986). The C4B null allele has been associated with increased viral and bacterial infections including bacterial meningitis (Rowe, McLean, Wood, Leggiardro, & Winkelstein, 1989), Streptococcus pneumoniae, Hemophilus influenzae, and Neisseria meningitidis (Bishof, Welch, & Beischel, 1990). The C4 genes along with other complement genes BF and C2 are located between the HLA-B region and HLA-DR region (Figure 1) of the MHC (Apler, Awdeh, & Yunis, 1989). Certain combinations of HLA-B, complement, and HLA-DR alleles associate together more often than would be expected from the relative distance between their respective loci and have been termed "extended MHC haplotypes" (Awdeh, Raum, Yunis, & Alper, 1983). The C4B null allele is recognized as part of one of these extended haplotypes designated [HLA-B44-SC30-DR4] in which the HLA-B allele is 44, the BF