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HLA complement gene polymorphisms in multiple sclerosis

A study on 80 Italian patients


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.

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  1. 1.

    Awdeh ZL, Alper CA (1980) Inherited structural polymorphism of the fourth component of human complement. Proc Natl Acad Sci USA 77:3576–3578

  2. 2.

    Barba G, Rittner C, Schneider PM (1993) Genetic basis of human complement C4 deficiency. J Clin Invest 91:1681–1686

  3. 3.

    Belt KT, Carroll MC, Porter RR (1984) The structural basis of the multiple forms of human complement component C4. Cell 36:907–914

  4. 4.

    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

  5. 5.

    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

  6. 6.

    Compston A (1986) Genetic factors in the aetiology of multiple sclerosis. In: McDonald WI, Silberberg DH (eds) Multiple sclerosis. Butterworths, London, pp 56–73

  7. 7.

    Compston A, Sadovnick AD (1992) Epidemiology and genetics of multiple sclerosis. Curr Opin Neurol Neurosurg 5:175–181

  8. 8.

    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

  9. 9.

    Dawkins RL, Christiansen FT, Kay PH, et al (1983) Disease associations with complotypes, supratypes and haplotypes. Immunol Rev 70:1–22

  10. 10.

    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

  11. 11.

    Geserick G, Abbal M, Brenden M (1990) Factor B (Bf) reference typing report. Complement Inflamm 7:183–189

  12. 12.

    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

  13. 13.

    Kurtzke JF (1983) Rating neurologic impairment in multiple sclerosis: an expanded disability status scale. Neurology 33:1444–1452

  14. 14.

    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

  15. 15.

    Larsen JP, Kvaale G, Riise T, Nyland H, Aarli JA (1985) Multiple sclerosis — more than one disease? Acta Neurol Scand 72:145–150

  16. 16.

    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

  17. 17.

    Mauff G, Alper CA, Dawkins R, et al (1990) C4 nomenclature statement. Complement Inflamm 7:261–268

  18. 18.

    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

  19. 19.

    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

  20. 20.

    Poser CM, Paty CW, Scheinberg L, et al (1983) New diagnostic criteria for multiple sclerosis: guidelines for research protocols. Ann Neurol 13:227–232

  21. 21.

    Rudge P (1991) Does a retrovirally encoded superantigen cause multiple sclerosis? J Neurol Neurosurg Psychiatry 54:853–855

  22. 22.

    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

  23. 23.

    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

  24. 24.

    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

  25. 25.

    Southern E (1975) Detection of specific sequences among DNA fragments separated by electrophoresis. J Mol Biol 98:503–517

  26. 26.

    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

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Correspondence to Diego Franciotta.

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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

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Key words

  • Multiple sclerosis Restriction fragment length polymorphisms
  • HLA class III genes
  • Complement component 4