Abstract
Based on evidence of an increased rate of respiratory infections in sudden infant death (SID) infants as well as the observation of familial occurrence, we analysed in a retrospective study class II and class III genes of the major histocompatibility complex in 40 cases of SID by Southern blot analysis of DNA obtained post mortem from tissue samples. In 24 cases, the parents were interviewed and confirmatory human lymphocyte antigen (HLA) and DNA typing was carried out. Using HLA-DRß and-DQß probes, no evidence of an abnormal HLA-DR frequency distribution in SID infants was detected (P=0.97). Using DNA probes for the tandemly arranged complement C4 and steroid 21-hydroxylase genes, an increased number of C4B gene deletions in SID cases was found. The increase in C4 gene deletions was significant (P=0.0125) in infants with recurrent infections. These data indicate a possible role of partial C4 deficiency as a genetically predisposing risk factor in SID.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
Abbreviations
- 21-OHA, 21-OHB:
-
the two genes for the cytochrome P450 steroid 21-hydroxylase (21-OHA is a pseudogene)
- BF:
-
factor B of the alternative pathway of complement
- C2:
-
the second component of complement
- C4A, C4B:
-
the two isotypes of the fourth component of complement
- C4 Q0:
-
null allele of C4 (no gene product detectable)
- EDTA:
-
Ethylendiamintetraacetate
- HLA:
-
human lymphocyte antigen
- MHC:
-
major histocompatibility complex
- RFLP:
-
restriction fragment length polymorphism
- SID:
-
sudden infant death
- SLE:
-
systemic lupus erythematosus
- SSPE:
-
subacute sclerosing panencephalitis
References
Althoff H (1980) Sudden infant death syndrome (SIDS). Fischer, Stuttgart
Althoff H (1987) Zur Bedeutung des plötzlichen Kindstodes (SIDS) für die Hals-, Nasen- und Ohrenheilkunde. HNO 35:430–434
Awdeh ZL, Alper CA (1980) Inherited structural polymorphism of the fourth component of human complement. Proc Natl Acad Sci USA 77:3576–3580
Baur MP, Neugebauer M, Deppe H, Sigmund M, Luton T, Mayr WR, Albert ED (1984) population analysis on the basis of deduced haplotypes from random families. In: Mayr ED, Baur MP, Albert ED (eds) Histocompatibility testing 1984. Springer, New York Berlin Heidelberg, pp 333–431
Belt KT, Carroll MC, Porter RR (1984) The structural basis of the multiple forms of human complement component C4. Cell 36: 907–914
Bidwell J (1988) DNA-RFLP analysis and genotyping of HLA-DR and DQ antigens. Immunol Today 9:18–23
Braun L, Schneider PM, Giles CM, Susemichel-Hüppner A, Bertrans J, Rittner C (1989) Analysis of complement C4 null alleles using PCR-amplified DNA gives evidence for gene conversion. Proceedings of the 7th International Congress of Immunology, Berlin, 30 July–5 August, 1989 (in press)
Carroll MC, Campbell RD, Bentley DR, Porter RR (1984) A molecular map of the human major histocompatibility complex class III region linking complement genes C4, C2 and factor B. Nature 307:237–241
Carroll MC, Campbell RD, Porter RR (1985) Mapping of steroid 21-hydroxylase genes adjacent to the complement component C4 genes in HLA, the major histocompatibility complex in man. Proc Natl Acad Sci USA 82:521–525
Carroll MC, Palsdottir A, Belt KT, Porter RR (1985) Deletion of complement C4 and steroid 21-hydroxylase genes in the HLA class III region. EMBO J 4:2547–2552
Cox NJ, Mela AP, Zmijewski CM, Spielman RS (1989) HLA-DR typing at the DNA level: RFLP's and subtypes detected with a DRß cDNA probe. Am J Hum Genet 43:954–963
Fielder AHL, Walport MJ, Batchelor JR, Rynes RI, Black CM, Dodi IA, Hughes GRV (1983) Family study of the major histocompatibility complex in patients with systemic lupus erythematosus: importance of null alleles of C4A and C4B in determining disease susceptibility. Br Med J 286:425–428
Forsyth KD, Weeks SC, Koh L, Skinner J, Bradley J (1989) Lung immunoglobulins in the sudden infant death syndrome. Br Med J 298:23–26
Gross-Bellard M, Oudet P, Chambon P (1973) Isolation of high molecular weight DNA from mammalian cells. Eur J Biochem 36:32–38
Horn M, Wehner HD, Heifer U, Rittner C (1986) Epidemiologische und immungenetische Untersuchungen zum plötzlichen und unerwarteten Säuglingstod (SIDS). Zentralbl Rechtsmed 29: 110–111
Huang SW (1983) Infectious diseases, immunology and SIDS: an overview. In: Tildon JT, Roeder LM, Steinschneider A (eds) Sudden infant death syndrome. Academic Press, New York, pp 593–606
Kemp ME, Atkinson JP, Skanes VM, Levine RP, Chaplin DD (1987) Deletion of C4A genes in patients with systemic lupus erythematosus. Arthritis Rheum 30:1015–1022
Lachmann PJ (1985) Antibody and complement in viral infections. Br Med Bull 41:3–6
Larhammer D, Schenning L, Gustafsson K, Wiman K, Claesson L, Rask L, Peterson PA (1982) Complete amino acid sequence of an HLA-DR antigen-like β chain as predicted from the nucleotide sequence: similarities with immunoglobulins and HLA-A,-B, and-C antigens. Proc Natl Acad Sci USA 79:3687–3691
Long EO, Wake CT, Gorski J, Mach B (1983) Complete sequence of an HLA-DR β chain deduced from a cDNA clone and identification of multiple non-allelic DR β chain genes. EMBO J 2:389–394
Mauff G, Alper CA, Awdeh ZL, Batchelor JR, Bertrams J, Bruun-Petersen G, Dawkins RL, Demant P, Edwards JH, Grosse-Wilde H, Hauptmann G, Klouda P, Lamm L, Mollenhauer E, Nerl C, Olaisen B, O'Neill G, Rittner C, Roos MH, Skanes V, Teisberg P, Wells L (1983) Statement on the nomenclature of human C4 allotypes. Immunobiology 164:184–191
Miura N, Prentice HL, Schneider PM, Perlmutter DH (1987) Synthesis and regulation of the two human complement C4 genes in stable transfected mouse fibroblasts. J Biol Chem 262:7298–7305
Palsdottir A, Cross SJ, Edwards JH, Carroll MC (1983) Correlation between a restriction fragment length polymorphism and C4A6 protein. Nature 306:615–616
Palsdottir A, Arnason A, Fossdal R, Jensson O (1987) Gene organization of haplotypes expressing two different C4A allotypes. Hum Genet 76:220–224
Riepert T, Schneider PM, Wendler C, Mattern R, Althoff H, Horn M, Rittner C (1989) Clinical, genetical, and epidemiological studies of sudden infant death syndrome (SIDS). Paediatrica (in press)
Rigby PWJ, Dieckmann M, Rhodes C, Berg P (1977) Labelling deoxynucleic acid to high specific activity in vitro by nick translation with DNA polymerase I. J Mol Biol 113:237–251
Rittner C, Meier EMM, Stradmann B, Giles CM, Köchling R, Mollenhauer E, Kreth HW (1984) Partial C4 deficiency in subacute sclerosing panencephalitis. Immunogenetics 20:407–415
Rittner C, Schneider PM (1988) Genetics and polymorphism of the complement components. In: Rother K, Till GO (eds) The complement system. Springer, New York Berlin Heidelberg, pp 80–135
Roos MH, Mollenhauer E, Demant P, Rittner C (1982) A molecular basis for the two locus model of human complement component C4. Nature 298:854–856
Rosenshine S, Cascino I, Zeevi A, Duquesnoy RJ, Trucco M (1986) DQ and β RFLP analysis reveals the composition of the DQ molecule recognized by T-cell clones. Immunogenetics 23: 187–196
Rother K, Till GO (eds) (1988) The complement system. Springer, New York Berlin Heidelberg
Schneider PM, Rittner C (1988) Bgl II restriction fragment polymorphism of human complement C4A gene coincides with BF*F allele of factor B. Immunogenetics 27:225–228
Schneider PM, Carroll MC, Alper CA, Rittner C, Whitehead AS, Yunis EJ, Colten HR (1986) Polymorphism of the human complement C4 and steroid 21-hydroxylase genes: restriction fragment length polymorphisms revealing structural deletions, homoduplications and size variants. J Clin Invest 78:650–657
Tait BD, Williams AL, Mathews JD, Cowling DC (1977) HLA and sudden infant death syndrome. Monogr Allergy 11:55–59
Terasaki PI, McClelland JD (1964) Microdroplet assay of human serum cytotoxins. Nature 204:998–1001
Tildon JT, Roeder LM, Steinschneider A (eds) (1983) Sudden infant death syndrome. Academic Press, New York
Tiwari JL, Terasaki PI (1985) HLA and disease associations. Springer, New York Berlin Heidelberg
White PC, Grossberger D, Onufer BJ, Chaplin DD, New MI, Dupont B, Strominger JL (1985) Two genes encoding steroid 21-hydroxylase are located near the genes encoding the fourth component of complement in man. Proc Natl Acad Sci USA 82:1089–1093
Whitehead AS, Woods DE, Fleichnick E, Chin JE, Yunis EJ, Katz AJ, Gerald PS, Alper CA, Colten HR (1984) DNA polymorphism of the C4 genes. A new marker for analysis of the major histocompatibility complex. N Engl J Med 310:88–91
Williams AL, Uren EC, Bretherton L (1984) Respiratory viruses and sudden infant death. Br Med J 288:1491–1493
Yu CY, Campbell RD (1987) Definitive RFLPs to distinguish between the human complement C4A/C4B isotypes and the major Rodgers/Chido determinants: application to the study of C4 null alleles. Immunogenetics 25:383–390
Zink P, Drescher J, Verhagen W, Flik J, Milbradt H (1987) Serological evidence of recent influenza A (H3N2) infections in forensic cases of the sudden infant death syndrome (SIDS). Arch Virol 93:223–232
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Schneider, P.M., Wendler, C., Riepert, T. et al. Possible association of sudden infant death with partial complement C4 deficiency revealed by post-mortem DNA typing of HLA class II and III genes. Eur J Pediatr 149, 170–174 (1989). https://doi.org/10.1007/BF01958273
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF01958273