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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

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

Truedsson L
Mol Immunol 2015 Nov;68(1):14-9. Epub 2015 May 30 doi: 10.1016/j.molimm.2015.05.007. PMID: 26038300
Boteva L, Morris DL, Cortés-Hernández J, Martin J, Vyse TJ, Fernando MM
Am J Hum Genet 2012 Mar 9;90(3):445-56. Epub 2012 Mar 1 doi: 10.1016/j.ajhg.2012.01.012. PMID: 22387014Free PMC Article
Yang Y, Chung EK, Zhou B, Lhotta K, Hebert LA, Birmingham DJ, Rovin BH, Yu CY
Curr Dir Autoimmun 2004;7:98-132. doi: 10.1159/000075689. PMID: 14719377
Cicardi M, Zingale LC, Pappalardo E, Folcioni A, Agostoni A
Medicine (Baltimore) 2003 Jul;82(4):274-81. doi: 10.1097/01.md.0000085055.63483.09. PMID: 12861105
Sullivan KE
Curr Opin Pediatr 1998 Dec;10(6):600-6. doi: 10.1097/00008480-199810060-00011. PMID: 9848020

Diagnosis

Tak AS, Satapathy J, Jana M, Sinha A, Jat KR, Bagri NK
Rheumatol Int 2022 Aug;42(8):1477-1482. Epub 2021 Jul 21 doi: 10.1007/s00296-021-04943-y. PMID: 34287686
Patel G, Pongracic JA
Allergy Asthma Proc 2019 Nov 1;40(6):441-445. doi: 10.2500/aap.2019.40.4267. PMID: 31690390
Gompels MM, Lock RJ, Abinun M, Bethune CA, Davies G, Grattan C, Fay AC, Longhurst HJ, Morrison L, Price A, Price M, Watters D
Clin Exp Immunol 2005 Mar;139(3):379-94. doi: 10.1111/j.1365-2249.2005.02726.x. PMID: 15730382Free PMC Article
Fries LF, O'Shea JJ, Frank MM
Clin Immunol Immunopathol 1986 Jul;40(1):37-49. doi: 10.1016/0090-1229(86)90067-x. PMID: 2941192
Nusinow SR, Zuraw BL, Curd JG
Med Clin North Am 1985 May;69(3):487-504. doi: 10.1016/s0025-7125(16)31028-8. PMID: 3892188

Therapy

Al-Rayes H, Al-Swailem R, Arfin M, Sobki S, Rizvi S, Tariq M
Lupus 2007;16(9):755-63. doi: 10.1177/0961203307079943. PMID: 17728372
Gompels MM, Lock RJ, Abinun M, Bethune CA, Davies G, Grattan C, Fay AC, Longhurst HJ, Morrison L, Price A, Price M, Watters D
Clin Exp Immunol 2005 Mar;139(3):379-94. doi: 10.1111/j.1365-2249.2005.02726.x. PMID: 15730382Free PMC Article
Cicardi M, Zingale LC, Pappalardo E, Folcioni A, Agostoni A
Medicine (Baltimore) 2003 Jul;82(4):274-81. doi: 10.1097/01.md.0000085055.63483.09. PMID: 12861105
Thorne JE, Hernandez MI, Rencic A, Nousari HC
Am J Ophthalmol 2002 Dec;134(6):932-4. doi: 10.1016/s0002-9394(02)01814-7. PMID: 12470777
Rynes RI
Clin Rheum Dis 1982 Apr;8(1):29-47. PMID: 6288318

Prognosis

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
Kolho KL, Paakkanen R, Lepistö A, Wennerstöm A, Meri S, Lokki ML
J Pediatr Gastroenterol Nutr 2016 Apr;62(4):567-72. doi: 10.1097/MPG.0000000000000984. PMID: 26398154
Gilliam BE, Wolff AE, Moore TL
J Clin Rheumatol 2007 Oct;13(5):256-60. doi: 10.1097/RHU.0b013e318156b9e3. PMID: 17921792
Cicardi M, Zingale LC, Pappalardo E, Folcioni A, Agostoni A
Medicine (Baltimore) 2003 Jul;82(4):274-81. doi: 10.1097/01.md.0000085055.63483.09. PMID: 12861105
Nusinow SR, Zuraw BL, Curd JG
Med Clin North Am 1985 May;69(3):487-504. doi: 10.1016/s0025-7125(16)31028-8. PMID: 3892188

Clinical prediction guides

Lintner KE, Patwardhan A, Rider LG, Abdul-Aziz R, Wu YL, Lundström E, Padyukov L, Zhou B, Alhomosh A, Newsom D, White P, Jones KB, O'Hanlon TP, Miller FW, Spencer CH, Yu CY
Ann Rheum Dis 2016 Sep;75(9):1599-606. Epub 2015 Oct 22 doi: 10.1136/annrheumdis-2015-207762. PMID: 26493816Free PMC Article
Zhu B, Zhu CF, Lin Y, Perkovic V, Li XF, Yang R, Tang XL, Zhu XL, Cheng XX, Li Q, Chen HY, Sun Y, Chen QW, Wang YJ
Ren Fail 2015 Apr;37(3):424-32. Epub 2014 Dec 24 doi: 10.3109/0886022X.2014.994408. PMID: 25539484
Kosaka S, Osada S, Kaneko T, Nishimura S, Kawana S
Clin Exp Dermatol 2013 Jul;38(5):492-5. doi: 10.1111/j.1365-2230.2012.04423.x. PMID: 23777490
Yang Y, Chung EK, Zhou B, Lhotta K, Hebert LA, Birmingham DJ, Rovin BH, Yu CY
Curr Dir Autoimmun 2004;7:98-132. doi: 10.1159/000075689. PMID: 14719377
Kölble K, Reid KB
Int Rev Immunol 1993;10(1):17-36. doi: 10.3109/08830189309051169. PMID: 8340675

Recent systematic reviews

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
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

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