We studied C4A, C4B, and Bf complement gene polymorphisms in 80 Italian patients with multiple sclerosis (MS). We observed a significantly higher frequency of C4AQ0 allele in patients with the relapsing-remitting form of MS than in ethnically homogeneous controls. Restriction fragment length polymorphism analysis by Southern blotting of the C4/CYP21 gene complex showed that a structural gene deletion was present in 45% of patients with the C4AQ0 allele. Our data support the hypothesis that relapsing-remitting MS and primarily chronic progressive MS are immunogenetically distinct diseases; further, complement factor abnormalities typical of autoimmune diseases could influence the pathogenesis of MS.
This is a preview of subscription content, log in to check access.
Buy single article
Instant access to the full article PDF.
Price includes VAT for USA
Subscribe to journal
Immediate online access to all issues from 2019. Subscription will auto renew annually.
This is the net price. Taxes to be calculated in checkout.
Awdeh ZL, Alper CA (1980) Inherited structural polymorphism of the fourth component of human complement. Proc Natl Acad Sci USA 77:3576–3578
Barba G, Rittner C, Schneider PM (1993) Genetic basis of human complement C4 deficiency. J Clin Invest 91:1681–1686
Belt KT, Carroll MC, Porter RR (1984) The structural basis of the multiple forms of human complement component C4. Cell 36:907–914
Braun L, Schneider PM, Giles CM, Bertrams J, Rittner C (1990) Null alleles of human complement C4. Evidence for pseudogenes at the C4A locus and for gene conversion at the C4B locus. J Exp Med 171:129–140
Carroll MC, Campbell RD, Porter RR (1985) Mapping of steroid 21-hydroxylase genes adjacent to complement component C4 genes in HLA, the Major Histocompatibility Complex in man. Proc Natl Acad Sci USA 82:521–525
Compston A (1986) Genetic factors in the aetiology of multiple sclerosis. In: McDonald WI, Silberberg DH (eds) Multiple sclerosis. Butterworths, London, pp 56–73
Compston A, Sadovnick AD (1992) Epidemiology and genetics of multiple sclerosis. Curr Opin Neurol Neurosurg 5:175–181
Confavreux C, Aimard G, Devic M (1980) Course and prognosis of multiple sclerosis assessed by the computerized data processing of 349 patients. Brain 103:281–300
Dawkins RL, Christiansen FT, Kay PH, et al (1983) Disease associations with complotypes, supratypes and haplotypes. Immunol Rev 70:1–22
De Paoli F, Cuccia Belvedere M, Martinetti M, Abbal M (1987) Human MHC class III genes, Bf and C4 polymorphism, complotypes and HLA class I and II associations in Lombardy population. Gene Geogr 1:121–127
Geserick G, Abbal M, Brenden M (1990) Factor B (Bf) reference typing report. Complement Inflamm 7:183–189
Jurgens R, Schadlich HJ, Karbe M, et al (1989) Association of major histocompatibility complex related complement components Bf, C2 and C4 with the course of disease in multiple sclerosis (abstract). Complement Inflamm [Suppl] 6:291
Kurtzke JF (1983) Rating neurologic impairment in multiple sclerosis: an expanded disability status scale. Neurology 33:1444–1452
14.La Mantia L, Illeni MT, Milanese C, Salmaggi A, Eoli M, Pellegris G, Nespolo A (1991) HLA antigens in Italian multiple sclerosis patients. Ital J Neurol Sci 12:81–86
Larsen JP, Kvaale G, Riise T, Nyland H, Aarli JA (1985) Multiple sclerosis — more than one disease? Acta Neurol Scand 72:145–150
Madigand M, Oger J-JF, Fauchet R, Sabouraud O, Genetet B (1982) HLA profiles in multiple sclerosis suggest two forms of disease and the existence of protective haplotypes. J Neurol Sci 53:519–529
Mauff G, Alper CA, Dawkins R, et al (1990) C4 nomenclature statement. Complement Inflamm 7:261–268
Olerup O, Hillert J, Fredrikson S, et al (1989) Primarily chronic progressive and relapsing/remitting multiple sclerosis: two immunogenetically distinct disease entities. Proc Natl Acad Sci USA 86:7113–7117
Partanen J, Koskimies S, Johansson E (1988) C4 null phenotypes among lupus erythematosus patients are predominantly the result of deletions covering C4 and closely linked 21-hydroxylase A genes. J Med Genet 25:387–391
Poser CM, Paty CW, Scheinberg L, et al (1983) New diagnostic criteria for multiple sclerosis: guidelines for research protocols. Ann Neurol 13:227–232
Rudge P (1991) Does a retrovirally encoded superantigen cause multiple sclerosis? J Neurol Neurosurg Psychiatry 54:853–855
Schneider PM, Carrol MC, Alper CA, et a1 (1986) Polymorphism of the human component C4 and steroid 21-hydroxylase genes: restriction fragment length polymorphisms revealing structural deletions, homoduplications and size variants. J Clin Invest 78:650–657
Schifferli JA, Ng YC, Peters DK (1986) The role of complement and its receptor in elimination of immune complexes. N Engl J Med 315:488–491
Schroeder R, Zander H, Andreas A, Mauff G (1983) Multiple sclerosis: immunogenetic analysis of sibpair doublecase families. II. Studies on the association of multiple sclerosis with C2, C4, Bf, C3, C6 and Gm polymorphisms. Immunobiology 164:160–170
Southern E (1975) Detection of specific sequences among DNA fragments separated by electrophoresis. J Mol Biol 98:503–517
26.Van Lambalgen R, Sanders EA, D'Amaro J (1986) Sex distribution, age of onset and HLA profiles in two types of multiple sclerosis. J Neurol Sci 76:13–21
About this article
Cite this article
Franciotta, D., Dondi, E., Bergamaschi, R. et al. HLA complement gene polymorphisms in multiple sclerosis. J Neurol 242, 64–68 (1995). https://doi.org/10.1007/BF00887817
- Multiple sclerosis Restriction fragment length polymorphisms
- HLA class III genes
- Complement component 4