U.S. flag

An official website of the United States government

Format

Send to:

Choose Destination

C4 Deficiency

MedGen UID:
859438
•Concept ID:
C3899844
•
Disease or Syndrome

Definition

Lack of production of functional C4 protein, due to a genetic defect requiring homozygous loss of both the C4A and C4B genetic paralogs. Approximately 75% of patients with a C4 deficiency will develop a severe systemic lupus erythematosus at an early age. Patients also present with frequent sinopulmonary infections often with Streptococcus pneumoniae. [from NCI]

Professional guidelines

PubMed

Technical and theoretical considerations in the HLA typing of amniotic fluid cells for prenatal diagnosis and paternity testing.
Pollack MS, Heagney SD, Braun D Jr, O'Neill GJ
Prenat Diagn 1981 Jul;1(3):183-95. doi: 10.1002/pd.1970010304. PMID: 6981107

Recent clinical studies

Etiology

Classical pathway deficiencies - A short analytical review.
Truedsson L
Mol Immunol 2015 Nov;68(1):14-9. Epub 2015 May 30 doi: 10.1016/j.molimm.2015.05.007. PMID: 26038300
Complement deficiency and autoimmunity.
Sullivan KE
Curr Opin Pediatr 1998 Dec;10(6):600-6. doi: 10.1097/00008480-199810060-00011. PMID: 9848020
Genetic risk factors for aPL syndrome.
Wilson WA, Gharavi AE
Lupus 1996 Oct;5(5):398-403. doi: 10.1177/096120339600500513. PMID: 8902769
HLA DRw8 and complement C4 deficiency as risk factors in primary biliary cirrhosis.
Manns MP, Bremm A, Schneider PM, Notghi A, Gerken G, Prager-Eberle M, Stradmann-Bellinghausen B, Meyer zum Büschenfelde KH, Rittner C
Gastroenterology 1991 Nov;101(5):1367-73. doi: 10.1016/0016-5085(91)90090-8. PMID: 1936808
Chido, Rodgers, and C4 deficiency.
O'Neill GJ, Berger R, Ballow M, Yunis EJ, Dupont B
Transplant Proc 1979 Dec;11(4):1941-3. PMID: 93815

Diagnosis

Hereditary and acquired angioedema.
Patel G, Pongracic JA
Allergy Asthma Proc 2019 Nov 1;40(6):441-445. doi: 10.2500/aap.2019.40.4267. PMID: 31690390
A tale of two rashes.
Richmond BW, Cole MB, Dash A, Eyler A, Boomershine CS
Am J Med 2011 May;124(5):414-7. doi: 10.1016/j.amjmed.2011.01.003. PMID: 21531230
Clinical characteristics of chronic idiopathic thrombocytopenia in Chinese children.
Wong MS, Chan GC, Ha SY, Lau YL
J Pediatr Hematol Oncol 2002 Nov;24(8):648-52. doi: 10.1097/00043426-200211000-00009. PMID: 12439037
Hereditary angioedema: a case with ascites yet no symptoms in the family.
Shinzato T, Nakamura H, Kuniyoshi T, Higashionna A, Uehara T, Oshiro J, Uechi H, Shikiya K, Sakugawa H, Kinjo F
Intern Med 1992 May;31(5):633-5. doi: 10.2169/internalmedicine.31.633. PMID: 1504426
Acute and rapidly progressive forms of glomerulonephritis in the elderly.
Montoliu J, Darnell A, Torras A, Revert L
J Am Geriatr Soc 1981 Mar;29(3):108-16. doi: 10.1111/j.1532-5415.1981.tb01971.x. PMID: 7204803

Therapy

A tale of two rashes.
Richmond BW, Cole MB, Dash A, Eyler A, Boomershine CS
Am J Med 2011 May;124(5):414-7. doi: 10.1016/j.amjmed.2011.01.003. PMID: 21531230
Clinical characteristics of chronic idiopathic thrombocytopenia in Chinese children.
Wong MS, Chan GC, Ha SY, Lau YL
J Pediatr Hematol Oncol 2002 Nov;24(8):648-52. doi: 10.1097/00043426-200211000-00009. PMID: 12439037
Hereditary angioedema type II--a study of two families.
Solé D, Leser PG, Naspitz CK
J Investig Allergol Clin Immunol 1992 Nov-Dec;2(6):318-22. PMID: 1342916
Complement system protein C4 and susceptibility to hydralazine-induced systemic lupus erythematosus.
Speirs C, Fielder AH, Chapel H, Davey NJ, Batchelor JR
Lancet 1989 Apr 29;1(8644):922-4. doi: 10.1016/s0140-6736(89)92506-3. PMID: 2565418
Inherited complement deficiency states and SLE.
Rynes RI
Clin Rheum Dis 1982 Apr;8(1):29-47. PMID: 6288318

Prognosis

Human Inborn Errors of Immunity in Pyoderma Gangrenosum: A Systematic Review.
Oprea Y, Antohi DR, Vague M, Delbourgo Patton C, Wu B, Ortega-Loayza AG
Am J Clin Dermatol 2024 Sep;25(5):701-716. Epub 2024 Jul 1 doi: 10.1007/s40257-024-00875-y. PMID: 38951460
Subacute cutaneous lupus erythematosus: 25-year evolution of a prototypic subset (subphenotype) of lupus erythematosus defined by characteristic cutaneous, pathological, immunological, and genetic findings.
Sontheimer RD
Autoimmun Rev 2005 Jun;4(5):253-63. Epub 2004 Nov 12 doi: 10.1016/j.autrev.2004.10.003. PMID: 15990071
Clinical characteristics of chronic idiopathic thrombocytopenia in Chinese children.
Wong MS, Chan GC, Ha SY, Lau YL
J Pediatr Hematol Oncol 2002 Nov;24(8):648-52. doi: 10.1097/00043426-200211000-00009. PMID: 12439037
Treatment-free remission in severe systemic lupus erythematosus following synchronization of plasmapheresis with subsequent pulse cyclophosphamide.
Euler HH, Schroeder JO, Harten P, Zeuner RA, Gutschmidt HJ
Arthritis Rheum 1994 Dec;37(12):1784-94. doi: 10.1002/art.1780371212. PMID: 7986225
C4 isotype deficiency in IgA nephropathy.
Welch TR, Berry A, Beischel LS
Pediatr Nephrol 1987 Apr;1(2):136-9. doi: 10.1007/BF00849283. PMID: 3153269

Clinical prediction guides

Nephrotic syndrome due to immunologically mediated hypocomplementic glomerulonephritis in a patient of Waldenström's macroglobulinemia.
Haraguchi S, Tomiyoshi Y, Aoki S, Sakemi T
Nephron 2002 Oct;92(2):452-5. doi: 10.1159/000063286. PMID: 12218329
Treatment-free remission in severe systemic lupus erythematosus following synchronization of plasmapheresis with subsequent pulse cyclophosphamide.
Euler HH, Schroeder JO, Harten P, Zeuner RA, Gutschmidt HJ
Arthritis Rheum 1994 Dec;37(12):1784-94. doi: 10.1002/art.1780371212. PMID: 7986225
Hereditary angioedema type II--a study of two families.
Solé D, Leser PG, Naspitz CK
J Investig Allergol Clin Immunol 1992 Nov-Dec;2(6):318-22. PMID: 1342916
C4 isotype deficiency in IgA nephropathy.
Welch TR, Berry A, Beischel LS
Pediatr Nephrol 1987 Apr;1(2):136-9. doi: 10.1007/BF00849283. PMID: 3153269
Screening for deficiencies in the classical and alternative pathways of complement by hemolysis in gel.
Truedsson L, Sjöholm AG, Laurell AB
Acta Pathol Microbiol Scand C 1981 Jun;89(3):161-6. doi: 10.1111/j.1699-0463.1981.tb02680.x. PMID: 7032205

Recent systematic reviews

Human Inborn Errors of Immunity in Pyoderma Gangrenosum: A Systematic Review.
Oprea Y, Antohi DR, Vague M, Delbourgo Patton C, Wu B, Ortega-Loayza AG
Am J Clin Dermatol 2024 Sep;25(5):701-716. Epub 2024 Jul 1 doi: 10.1007/s40257-024-00875-y. PMID: 38951460
AA Amyloidosis Secondary to Primary Immune Deficiency: About 40 Cases Including 2 New French Cases and a Systematic Literature Review.
Delplanque M, Galicier L, Oziol E, Ducharme-Bénard S, Oksenhendler E, Buob D, Grateau G, Boutboul D, Georgin-Lavialle S
J Allergy Clin Immunol Pract 2021 Feb;9(2):745-752.e1. Epub 2020 Sep 30 doi: 10.1016/j.jaip.2020.09.023. PMID: 33007500

Supplemental Content

Table of contents

    Practice guidelines

    • PubMed
      See practice and clinical guidelines in PubMed. The search results may include broader topics and may not capture all published guidelines. See the FAQ for details.

    Related information

    • PMC Articles
      Related information in PubMed Central Links
    • PubMed
      Related literature resources in PubMed

    Recent activity

    Clear Turn Off Turn On

    Your browsing activity is empty.

    Activity recording is turned off.

    Turn recording back on

    See more...