Advertisement

Journal of Clinical Immunology

, Volume 2, Issue 2, pp 110–117 | Cite as

Partial H (β1H) deficiency and glomerulonephritis in two families

  • Robert J. Wyatt
  • Bruce A. Julian
  • Arthur Weinstein
  • Naomi F. Rothfield
  • Robert H. McLean
Original Articles

Abstract

H (β1H) controls the C3b amplification loop by its ability to displace Bb from the alternative pathway convertase, C3b,Bb, and acts as a cofactor with I (C3b inactivator) to produce inactive C3b. Serum C3 levels are dependent to a large extent on the levels of H and I. Partial H deficiency was found in two families. The index case in Family 1 had vasculitis, thrombocytopenia, proteinuria, and depressed serum H and C3 levels. The index case in Family 2 had depressed serum H and B (Factor B) levels and IgA nephropathy which progressed to renal failure. His sister also had IgA nephropathy and depressed serum H and C3 levels. The depressed serum C3 level, B level, and H level could be responsible for the development of the immune diseases found in some members of these families.

Key words

Complement C3 IgA nephropathy 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Ruddy S, Gigli I, Austen KF: The complement system of man. N Engl J Med 287:592–596, 1972Google Scholar
  2. 2.
    Agnello V, de Bracco MME, Kunkel HG: Hereditary C2 deficiency with some manifestations of systemic lupus erythematosus. J Immunol 108:837–840, 1972Google Scholar
  3. 3.
    Day NK, Geiger H, McLean R, Michael A, Good RA: C2 deficiency. Development of lupus erythematosus. J Clin Invest 52:1601–1607, 1973Google Scholar
  4. 4.
    Glass D, Raum D, Gibson D, Stillman JS, Schur PH: Inherited deficiency of the second component of complement. Rheumatic disease associations. J Clin Invest 58:853–861, 1976Google Scholar
  5. 5.
    Hanuptman G, Grosshans E, Heid E: Lupus erythemateus aïgus et déficits héréditaires en complement. A propos d'un cas par déficit complet en C4. Ann Dermatol Syph 101:479–488, 1974Google Scholar
  6. 6.
    Ochs HD, Rosenfeld SI, Thomas ED, Giblett ER, Alper CA, Dupont B, Schaller JG, Gilliland BC, Hansen JA, Wedgewood, RJ: Linkage between the gene (or genes) controlling synthesis of the fourth component of complement and the major histocompatibility complex. N Engl J Med 296:470–475, 1977Google Scholar
  7. 7.
    Pickering RJ, Michael AF, Herdman RC, Good RA, Gewurz H: The complement system in chronic glomerulonephritis: Three newly associated aberrations. J Pediat 78:30–43, 1971Google Scholar
  8. 8.
    Kim Y, Friend PS, Dresner IG, Yunis EJ, Michael AF: Inherited deficiency of the second component of complement (C2) with membranoproliferative glomerulonephritis. Am J Med 62:765–771, 1977Google Scholar
  9. 9.
    Pussell BA, Bourke E, Nayef M, Morris S, Peters DK: Complement deficiency and nephritis. A report of a family. Lancet 1:675–677, 1980Google Scholar
  10. 10.
    Coleman TH, Forristal J, West CD: Hereditary C6 deficiency in membranoproliferative glomerulonephritis type 1. Pediat Res 13:446, 1979Google Scholar
  11. 11.
    Sussman M, Jones JH, Almeida JD, Lachman PJ: Deficiency of the second component of complement associated with anaphylactoid purpura and presence of mycoplasma in the serum. Clin Exp Immunol 14:531–539, 1973Google Scholar
  12. 12.
    Gelfand EW, Clarkson JE, Minta JO: Selective deficiency of the second component of complement in a patient with anaphylactoid purpura. Clin Immunol Immunopathol 4:269–276, 1975Google Scholar
  13. 13.
    Einstein LP, Alper CA, Bloch KJ, Herrin JT, Rosen FS, David JR, Colten HR: Biosynthetic defect in monocytes from human beings with genetic deficiency of the second component of complement. N Engl J Med 292:1169–1173, 1975Google Scholar
  14. 14.
    Evans DG, Gwyn Williams D, Peters DK, Sissons JGP, Boulton-Jones JM, Ogg CS, Cameron JS, Hoffbrand BI: Glomerular deposition of properdin in Henoch-Schönlein syndrome and idiopathic focal nephritis. Br Med J 3:326–328, 1973Google Scholar
  15. 15.
    Weiss JH, Bhathena DB, Curtis JJ, Lucas BA, Luke RG: A possible relationship between Henoch-Schönlein syndrome and IgA nephropathy (Berger's disease). An illustrative case. Nephron 22:582–591, 1978Google Scholar
  16. 16.
    McLean RH, Weinstein A, Chapitis J, Lowenstein M, Rothfield NF: Familial partial deficiency of the third component of complement (C3) and the hypocomplementemic cutaneous vasculitis syndrome. Am J Med 68:549–558, 1980Google Scholar
  17. 17.
    Whaley K, Ruddy S: Modulation of the alternative complement pathway by β1H globulin. J Exp Med 144:1147–1163, 1976Google Scholar
  18. 18.
    Weiler JM, Daha MR, Austen KF, Fearon DT: Control of the amplificating convertase of complement by the plasma protein β1H. Proc Natl Acad Sci USA 73:3268–3272, 1976Google Scholar
  19. 19.
    Fearon DT, Austen KF: Activation of the alternative complement pathway due to resistance of zymosan bound amplification convertase to endogenous regulatory mechanisms. Proc Natl Acad Sci USA 74:1683–1687, 1977Google Scholar
  20. 20.
    Fearon DT, Austen KF: Activation of the alternative complement pathway with rabbit erythrocytes by circumvention of the regulatory action of endogenous control proteins. J Exp Med 146:22–33, 1977Google Scholar
  21. 21.
    McLean RH, Weinstein A, Damjanov T, Rothfield N: Hypomorphic variant of C3, arthritis and chronic glomerulonephritis. J Pediat 93:937–943, 1978Google Scholar
  22. 22.
    Wyatt RJ, Forristal J, Davis CA, Coleman TH, West CD: Control of serum C3 levels by β1H and C3b inactivator. J Lab Clin Med 95:905–917, 1980Google Scholar
  23. 23.
    Bartlow BG, Roberts JL, Lewis EJ: Nonimmunoglobulin C3 activating factor in membranoproliferative glomerulonephritis. Kidney Int 15:294–302, 1979Google Scholar
  24. 24.
    Strife CF, McDonald BM, Ruley EJ, McAdams AJ, West CD: Shunt nephritis: The nature of the serum cryoglobulins and their relation to the complement profile. J Pediat 88:403–413, 1976Google Scholar
  25. 25.
    Wyatt RJ, Bridges RB, Halatek DG: Complement levels in cigarette smokers: Elevation of serum concentration of C5, C9, 116-1-inhibitor. J Clin Lab Immunol 6:131–135, 1981Google Scholar
  26. 26.
    Ruley EJ, Forristal J, Davis NC, Andres C, West CD: Hypocomplementemia of membranoproliferative nephritis. Dependence of the nephritic factor reaction on properdin factor B. J Clin Invest 52:896–904, 1973Google Scholar
  27. 27.
    Hay FC, Nineham LJ, Roitt IM: Routine assay for the detection of immune complexes of known immunoglobulin class using solid phase Clq. Clin Exp Immunol 24:396–400, 1976Google Scholar
  28. 28.
    Abrass CK, Hall CL, Border WA, Brown CA, Glassock RJ, Coggins CH: Circulating immune complexes in adults with idiopathic nephrotic syndrome. Kidney Int 17:545–553, 1980Google Scholar
  29. 29.
    Casali P, Lambert PH: Purification of soluble immune complexes from serum using polymethylmetacrylate beads coated with conglutinin or Clq. Application to the analysis ofin vitro formed immune complexes and of immune complexes occurringin vivo during Leishmaniasis. Clin Exp Immunol 37:295–309, 1979Google Scholar
  30. 30.
    Schreiber RD, Pangburn MK, LeSavre PH, Müller-Eberhard HJ: Initiation of alternative pathway of complement: Recognition of activators by bound C3b and assembly of the entire pathway from six isolated proteins. Proc Natl Acad Sci USA 75:3948–3952, 1978Google Scholar
  31. 31.
    Nydegger UE, Fearon DT, Austen KF: The modulation of the alternative pathway of complement in C2 deficient human serum by changes in concentration of the component and control proteins. J Immunol 120:1404–1408, 1978Google Scholar
  32. 32.
    Whaley K, Widner H, Ruddy S: Modulation of the alternative pathway amplification loop in rheumatic disease.In Clinical Aspects of the Complement System, W Opferkuch (ed). Stuttgart, Georg Thieme, 1978, pp 99–111Google Scholar
  33. 33.
    Whaley K, Schur PH, Ruddy S: Relative importance of C3b inactivator and β1H globulin in the modulation of the properdin amplification loop in systemic lupus erythematosus. Clin Exp Immunol 36:408–414, 1979Google Scholar
  34. 34.
    Aguado MT, Perrin LH, Ramirez PA, Miescher PA, Lambert P-H: Evaluation of alternative pathway and factor B haemolytic activities in patients with systemic lupus erythematosus: Correlations with the alternative pathway regulatory proteins. Clin Exp Immunol 42:495–505, 1980Google Scholar
  35. 35.
    Charlesworth A, Scott DM, Pussell BA, Peters DK: Metabolism of human β1H: Studies in man and animals. Clin Exp Immunol 38:397–404, 1979Google Scholar
  36. 36.
    Berger J: IgA glomerular deposits in renal disease. Transplant Proc 1:939–944, 1969Google Scholar
  37. 37.
    Lowance DG, Mullins JD, McPhaull JJ: Immunoglobulin A (IgA) associated glomerulonephritis. Kidney Int 3:167–176, 1973Google Scholar
  38. 38.
    Levy M, Beaufils H, Gubler MC, Habib R: Idiopathic recurrent macroscopic hematuria and mesangial IgA-IgG deposits in children (Berger's disease). Clin Nephrol 1:63–69, 1973Google Scholar
  39. 39.
    de Werra P, Morel-Maroger L, Leroux-Robert C, Richet G: Glomerulités à dépôts d'IgA diffus dans le mésangium. Schweiz Med Wschr 103:761–768, 797–803, 1973Google Scholar
  40. 40.
    McCoy RC, Abramowsky CR, Tisher CC: IgA nephropathy. Am J Pathol 76:123–144, 1974Google Scholar
  41. 41.
    Sinniah R, Law CH, Pwee HS: Glomerular lesions in patients with asymptomatic persistent and orthostatic proteinuria discovered on routine medical examination. Clin Nephrol 7:1–14, 1977Google Scholar
  42. 42.
    Droz D: Natural history of primary glomerulonephritis with mesangial deposits of IgA. Cont Nephrol 2:150–157, 1976Google Scholar
  43. 43.
    Clarkson AR, Seymour AE, Thompson AJ, Haynes WDG, Chan YL, Jackson B: IgA nephropathy: A syndrome of uniform morphology, diverse clinical features and uncertain prognosis. Clin Nephrol 8:459–471, 1977Google Scholar
  44. 44.
    Berger J, Yaneva H, Crosnier J: La glomérulonéphrite à dépôts mésangiaux d'IgA: Une cause fréquente d'insuffisance rénale terminale. Nouv Presse Med 9:219–221, 1980Google Scholar
  45. 45.
    Davies DR, Tighe JR, Jones NF, Brown GW: Recurrent hematuria and mesangial IgA deposition. J Clin Pathol 26:672–677, 1973Google Scholar
  46. 46.
    McEnery PT, McAdams AJ, West CD: Glomerular morphology, natural history and treatment of children with IgA-IgG mesangial nephropathy.In Glomerulonephritis: Morphology, Natural History and Treatment, P Kincaid-Smith, TH Mathew, EL Becker (eds). New York, Wiley, 1973, pp 305–320Google Scholar
  47. 47.
    Sissons JGP, Woodrow DF, Curtis JR, Evans DJ, Gower PE, Sloper JC, Peters DK: Isolated glomerulonephritis with mesangial IgA deposits. Br Med J 3:611–614, 1975Google Scholar
  48. 48.
    Zimmerman SW, Burkholder PM: Immunoglobulin A nephropathy. Arch Intern Med 135:1217–1223, 1975Google Scholar
  49. 49.
    Katz A, Underdown BJ, Minto JO, Lepow IH: Glomerulonephritis with mesangial deposits of IgA unassociated with systemic disease. Can Med Assoc J 114:209–215, 1976Google Scholar
  50. 50.
    van der Peet J, Arisz L, Brentjens JRH, Marrink J, Hoedemaeker J: The clinical course of IgA nephropathy in adults. Clin Nephrol 8:335–350, 1977Google Scholar
  51. 51.
    Bradley GE, Bailey RR, McGiven AR, Day WA: IgA nephropathy: A report of three cases. NZ Med J 83:219–222, 1976Google Scholar
  52. 52.
    Joshua H, Sharon Z, Gutglas E, Rosenfeld J, Ben-Bassat M: IgA-IgG nephropathy. A clinicopathologic entity with slow evolution and favorable prognosis. Am J Clin Pathol 67:289–295, 1977Google Scholar
  53. 53.
    Tolkoff-Rubin NE, Cosimi AB, Fuller T, Rubin RH, Colvin RB: IgA nephropathy in HLA-identical siblings. Transplantation 26:430–433, 1978Google Scholar
  54. 54.
    Okada M, Tsuchida H, Yamamoto S: Familial mesangial IgA nephropathy.In Glomerulonephritis, Y Yoshitoshi, Y Ueda (eds). Baltimore, University Park Press, 1979, pp 201–223Google Scholar
  55. 55.
    Sabatier J, Genin C, Assenat H, Colon S, Ducret F, Bertoux FC: Mesangial IgA glomerulonephritis in HLA-identical brothers. Clin Nephrol 11:35–38, 1979Google Scholar
  56. 56.
    Katz A, Caranicolas S, Falk JA: Family study in IgA nephritis: The possible role of HLA antigens. Transplantation 29:505–506, 1980Google Scholar
  57. 57.
    Montoliu J, Darnell A, Torras A, Ercilla G, Valles M, Revert L: Familial IgA nephropathy. Report of two cases and brief review of the literature. Arch Intern Med 140:1374–1375, 1980Google Scholar
  58. 58.
    Belton P, Carmody M, Donohue J, O'Dwyer WF: IgA nephropathy (Berger's disease): A clinical study of 32 cases. Irish J Med Sci 149:310–314, 1980Google Scholar
  59. 59.
    Spichtin HP, Truniger B, Mihatsch MJ, Bucher U, Gudat F, Zollinger HU: Immunothrobocytopenia and IgA nephritis. Clin Nephrol 14:304–308, 1980Google Scholar
  60. 60.
    Woodroffe AJ, Gormly AA, McKenzie PE, Wootton AM, Thompson AJ, Seymour AE, Clarkson AR: Immunologic studies in IgA nephropathy. Kidney Int 18:366–374, 1980Google Scholar

Copyright information

© Plenum Publishing Corporation 1982

Authors and Affiliations

  • Robert J. Wyatt
    • 1
  • Bruce A. Julian
    • 2
  • Arthur Weinstein
    • 3
  • Naomi F. Rothfield
    • 3
  • Robert H. McLean
    • 4
  1. 1.Department of PediatricsUniversity of Kentucky College of MedicineLexington
  2. 2.Department of MedicineUniversity of Kentucky College of MedicineLexington
  3. 3.Department of MedicineUniversity of Connecticut Health CenterFarmington
  4. 4.Department of PediatricsThe Johns Hopkins University School of MedicineBaltimore

Personalised recommendations