Genetic deficiency of the second component of complement (C2) associated with systemic lupus erythematosus

Relation of the complement abnormality and disease manifestations
      This paper is only available as a PDF. To read, Please Download here.


      Systemic lupus erythematosus (SLE) was documented in a patient with genetic deficiency of the second complement component (C2). A review of disease manifestations in this patient and in others with SLE and genetic C2 deficiency previously reported on suggest that many findings such as fever, skin lesions, central nervous system involvement, the presence of autoantibodies and leukopenia occur in patients with SLE independent of whether or not they have C2 deficiency. However, renal disease appears mild in patients with genetic C2 deficiency despite the presence of immunoglobulins and complement components demonstrated in glomeruli by immunofluorescent microscopy. Electron microscopic study of glomeruli from the patient we describe showed electron-dense deposits consistent with the immunofluorescent findings. Tubuloreticular inclusion bodies identical to those previously seen in patients with SLE were also observed. Analysis of serum complement components and tissue deposition of complement components suggests activation of both the classic and alternative complement pathways in patients with C2 deficiency. The clinical, pathologic and complement findings in this group of patients support the hypothesis that although SLE is similar in patients with and without C2 deficiency, renal disease remains mild when this classic pathway component is not present. Histocompatibility antigen analysis of the family of the propositus confirmed the association of C2 deficiency with an A10, B18 haplotype, and with a haplotype not previously associated with C2 deficiency, AW32, BW40. One sibling with this latter haplotype has normal C2 levels, presumably as a result of recombination.
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to The American Journal of Medicine
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Klemperer MR
        • Woodworth HC
        • Rosen FS
        • et al.
        Hereditary deficiency of the second component of complement (C2) in man.
        J Clin Invest. 1966; 45: 880
        • Pickering RJ
        • Michael Jr, AF
        • Herdman RC
        • et al.
        The complement system in chronic glomerulonephritis. Three newly associated aberrations.
        J Pediatr. 1971; 78: 30
        • Day NK
        • Geiger H
        • McLean R
        • et al.
        C2 deficiency development of lupus erythematosus.
        J Clin Invest. 1973; 52: 1601
        • Agnello V
        • DeBracco MM
        • Kunkel HG
        Hereditary C2 deficiency with some manifestations of systemic lupus erythematosus.
        J Immunol. 1972; 108: 837
        • Sussman M
        • Jones JH
        • Almeida JD
        • et al.
        Deficiency of the second component of complement associated with anaphylactoid purpura and presence of mycoplasma in the serum.
        Clin Exp Immunol. 1973; 14: 531
        • Einstein LP
        • Alper CA
        • Bloch KJ
        • et al.
        Biosynthetic defect in monocytes from human beings with genetic deficiency of the second component of complement.
        J Engl J Med. 1975; 292: 1169
        • Wolski KP
        • Schmid FR
        • Mittal KK
        Genetic linkage between HL-A system and a deficit of the second component (C2) of complement.
        Science. 1975; 188: 1020
        • Osterland CK
        • Espinoza L
        • Parker LP
        Inherited C2 deficiency and systemic lupus erythematosus. Studies on a family.
        Ann Intern Med. 1975; 82: 323
        • Leddy JP
        • Griggs RC
        • Klemperer MR
        • et al.
        Hereditary complement (C2) deficiency with dermatomyositis.
        Am J Med. 1975; 58: 83
        • Friend P
        • Repine JE
        • Kim Y
        • et al.
        Deficiency of the second component of complement (C2) with chronic vasculitis.
        Ann Intern Med. 1975; 83: 813
        • Wild JH
        • Zvaifler NJ
        • Müller-Eberhard HJ
        • et al.
        C3 metabolism in a patient with deficiency of the second component of complement (C2) and discoid lupus erythematosus.
        Clin Exp Immunol. 1967; 24: 238
        • Fu SM
        • Kunkel HG
        • Brusman HP
        • et al.
        Evidence for linkage between HL-A histocompatibility genes and those involved in the synthesis of the second component of complement.
        J Exp Med. 1974; 140: 1108
        • Müller-Eberhard HJ
        Annu Rev Biochem. 1975; 44: 697
        • Schur PH
        • Austen KF
        Complement in the rheumatic diseases.
        Bull Rheum Dis. 1971–1972; 22: 666
        • Morse JH
        • Müller-Eberhard HJ
        • Kunkel HG
        Antinuclear factors and serum complement in systemic lupus erythematosus.
        Bull NY Acad Med. 1962; 38: 641
        • Gewurz H
        • Pickering RJ
        • Mergenhagen SE
        • et al.
        The complement profile in acute glomerulonephritis, systemic lupus erythematosus and hypocomplementemic chronic glomerulonephritis. Contrasts and experimental correlations.
        Int Arch Allergy Appl Immunol. 1968; 34: 556
        • Kohler PF
        • TenBensel R
        Serial complement component alterations in acute glomerulonephritis and systemic lupus erythematosus.
        Clin Exp Immunol. 1969; 4: 191
        • Schur PH
        • Sandson J
        Immunologic factors and clinical activity in systemic lupus erythematosus.
        N Engl J Med. 1968; 278: 533
        • Lewis EJ
        • Busch GJ
        • Schur PH
        Gamma G globulin subgroup composition of the glomerular deposits in human renal diseases.
        J Clin Invest. 1970; 49: 1103
        • Lewis EJ
        • Carpenter CB
        • Schur PH
        Serum complement component levels in human glomerulonephritis.
        Ann Intern Med. 1971; 75: 555
        • Petz LD
        • Sharp GC
        • Cooper NR
        • et al.
        Serum and cerebral spinal fluid complement and serum autoantibodies in systemic lupus erythematosus.
        Medicine (Baltimore). 1971; 50: 259
        • Hadler NM
        • Gerwin RD
        • Frank MM
        The fourth component of complement in the cerebrospinal fluid in systemic lupus erythematosus.
        Arthritis Rheum. 1973; 16: 507
        • Hunsicker LG
        • Ruddy S
        • Carpenter CB
        • et al.
        Metabolism of third complement component (C3) in nephritis. Involvement of the classic and alternate (properdin) pathways for complement activation.
        N Engl J Med. 1972; 287: 835
        • Perrin LH
        • Lambert PH
        • Miescher PA
        Properdin levels in systemic lupus erythematosus and membrano-proliferative glomerulonephritis.
        Clin Exp Immunol. 1974; 16: 575
        • McLean RH
        • Michael AF
        Properdin and C3 proactivator. Alternate pathway components in human glomerulonephritis.
        J Clin Invest. 1974; 52: 634
        • Rothfield NF
        • Ross HA
        • Minta JO
        • et al.
        Glomerular and dermal deposition of properdin in systemic lupus erythematosus.
        N Engl J Med. 1972; 287: 681
        • Phillips PE
        The virus hypothesis in systemic lupus erytheatosus.
        Ann Intern Med. 1975; 83: 709
        • Tonnietti G
        • Oldstone MBA
        • Dixon FJ
        The effect of induced chronic viral infection on the immunological diseases of New Zealand mice.
        J Exp Med. 1970; 132: 89
        • Lewis RM
        • Andre-Schwartz J
        • Harris GS
        • et al.
        Canine systemic lupus erythematosus. Transmission of serologic abnormalities by cell-free filtrates.
        J Clin Invest. 1973; 52: 1893
        • Gyorkey F
        • Min KW
        • Sincovics JG
        • et al.
        Systemic lupus erythematosus and myxovirus.
        N Engl J Med. 1969; 280: 333
        • Norton WL
        Endothelial inclusions in active lesions of systemic lupus erythematosus.
        J Lab Clin Med. 1969; 74: 369
        • Ruddy S
        • Gigli I
        • Austen KF
        The complement system of man.
        N Engl J Med. 1972; 287: 489
        • Gewurz H
        • Page AR
        • Pickering RJ
        • et al.
        Complement activity and inflammatory neutrophil exudation in man. Studies in patients with glomerulonephritis, essential hypocomplementemia and agammaglobulinemia.
        Int Arch Allergy. 1967; 32: 64
        • Pickering RJ
        • Gewurz H
        • Kelly JR
        • et al.
        The complement system in hereditary angioneurotic edema. A new perspective.
        Clin Exp Immunol. 1968; 3: 423
        • Mancini G
        • Carbonara AO
        • Heremans JF
        Immunochemical quantitation of antigens by single radial immunodiffusion.
        Immunochemistry. 1965; 2: 235
        • Hanauer LB
        • Christian CL
        Clinical studies of hemolytic complement and the 11S component.
        Am J Med. 1967; 42: 882
        • Axelson NH
        • Kroll J
        • Weeke B
        Quantitative Immunoelectrophoresis Methods and Applications.
        in: Univirsitetsforloget, Oslo1973: 17
        • Cohen AS
        • Reynolds WE
        • Franklin EC
        Preliminary criteria for the classification of systemic lupus erythematosus.
        Bull Rheum Dis. 1971; 21: 643
        • Notman DD
        • Kurata N
        • Tan EM
        Profiles of antinuclear antibodies in systemic rheumatic diseases.
        Ann Intern Med. 1975; 83: 464
        • Agnello V
        • Koffler D
        • Eisenberg JW
        • et al.
        C1q precipitins in the sera of patients with systemic lupus erythematosus and other hypocomplementemic states.
        J Exp Med. 1971; 134 (suppl): 228s
        • Alper CA
        • Rosen FS
        Studies of the in vivo behavior of human C3 in normal subjects and patients.
        J Clin Invest. 1967; 46: 2021
        • Carpenter CB
        • Ruddy S
        • Shehadeh IH
        • et al.
        Complement metabolism in man. Hypercatabolism of the fourth (C4) and third (C3) components in patients with renal allograft rejection and hereditary angioedema (HAE).
        J Clin Invest. 1969; 48: 1495
        • Sliwinski AJ
        • Zvaifler NJ
        Decreased synthesis of the third component of complement (C3) in hypocomplementemic systemic lupus erythematosus.
        Clin Exp Immunol. 1972; 11: 21
        • Charlesworth JA
        • Williams DG
        • Sherington E
        • et al.
        Metabolic studies of the third component of complement and the glycine-diet beta glycoprotein in patients with hypocomplementemia.
        J Clin Invest. 1974; 53: 1578
        • Sergent JS
        • Christian CL
        Necrotizing vasculitis after acute serous otitis media.
        Ann Intern Med. 1974; 81: 195
        • Grimley PM
        • Schaff Z
        Significance of tubuloreticular inclusions in the pathobiology of human disease.
        Pathobiol Annu. 1976; 6: 221
        • Tisher CC
        • Kelso HB
        • Robinson RR
        • et al.
        Intraendothelial inclusions in kidneys of patients with systemic lupus erythematosus.
        Ann Intern Med. 1971; 75: 537
        • Fu SM
        • Kunkel HG
        Association of C2 deficiency and HL-A haplotype 10, W18.
        Transplantation. 1975; 20: 179
        • Day NK
        • L'Esperance R
        • Good RA
        • et al.
        Hereditary C2 deficiency. Genetic studies and association with HL-A system.
        J Exp Med. 1975; 141: 1464
        • Friend PS
        • Handwerger BS
        • Kim Y
        • et al.
        C2 deficiency in man. Genetic relationship to a mixed lymphocyte reaction determinant (7a*).
        Immunogenetics. 1975; 2: 569