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Immunodeficiency due to a classical component pathway complement deficiency

MedGen UID:
585054
•Concept ID:
C0398750
•
Disease or Syndrome
Synonyms: Classical complement pathway abnormality; immunodeficiency due to a C1, C4, or C2 component complement deficiency; immunodeficiency due to a classical component pathway complement deficiency; Immunodeficiency due to an early component of complement deficiency; immunodeficiency due to an early component of complement deficiency; Immunodeficiency due to C1, C4, or C2 component complement deficiency; immunodeficiency due to C1, C4, or C2 component complement deficiency
SNOMED CT: Classical complement pathway abnormality (234593008)
 
Monarch Initiative: MONDO:0015699
Orphanet: ORPHA169147

Definition

Immunodeficiency due to a classical component pathway complement deficiency is a primary immunodeficiency due to a deficiency in either complement components C1q, C1r, C1s, C2 or C4 characterized by increased susceptibility to bacterial infections, particularly with encapsulated bacteria, and increased risk for autoimmune disease. Most commonly, these include systemic lupus erythematosus (SLE), SLE-like disease, Henoch-Schonlein purpura, polymyositis and arthralgia. Disease severity is variable and dependent on the complement affected. [from ORDO]

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVImmunodeficiency due to a classical component pathway complement deficiency

Professional guidelines

PubMed

European Society for Immunodeficiencies (ESID) and European Reference Network on Rare Primary Immunodeficiency, Autoinflammatory and Autoimmune Diseases (ERN RITA) Complement Guideline: Deficiencies, Diagnosis, and Management.
Brodszki N, Frazer-Abel A, Grumach AS, Kirschfink M, Litzman J, Perez E, Seppänen MRJ, Sullivan KE, Jolles S
J Clin Immunol 2020 May;40(4):576-591. Epub 2020 Feb 17 doi: 10.1007/s10875-020-00754-1. PMID: 32064578Free PMC Article
Complement deficiencies and dysregulation: Pathophysiological consequences, modern analysis, and clinical management.
Schröder-Braunstein J, Kirschfink M
Mol Immunol 2019 Oct;114:299-311. Epub 2019 Aug 14 doi: 10.1016/j.molimm.2019.08.002. PMID: 31421540
Recombinant human complement component C2 produced in a human cell line restores the classical complement pathway activity in-vitro: an alternative treatment for C2 deficiency diseases.
Martini PG, Cook LC, Alderucci S, Norton AW, Lundberg DM, Fish SM, Langsetmo K, Jönsson G, Lood C, Gullstrand B, Zaleski KJ, Savioli N, Lottherand J, Bedard C, Gill J, Concino MF, Heartlein MW, Truedsson L, Powell JL, Tzianabos AO
BMC Immunol 2010 Aug 20;11:43. doi: 10.1186/1471-2172-11-43. PMID: 20727163Free PMC Article

Recent clinical studies

Etiology

Strong Association of Combined Genetic Deficiencies in the Classical Complement Pathway With Risk of Systemic Lupus Erythematosus and Primary Sjögren's Syndrome.
Lundtoft C, Sjöwall C, Rantapää-Dahlqvist S, Bengtsson AA, Jönsen A, Pucholt P, Wu YL, Lundström E, Eloranta ML, Gunnarsson I, Baecklund E, Jonsson R, Hammenfors D, Forsblad-d'Elia H, Eriksson P, Mandl T, Bucher S, Norheim KB, Auglaend Johnsen SJ, Omdal R, Kvarnström M, Wahren-Herlenius M, Truedsson L, Nilsson B, Kozyrev SV, Bianchi M, Lindblad-Toh K; DISSECT consortium, the ImmunoArray consortium, Yu CY, Nordmark G, Sandling JK, Svenungsson E, Leonard D, Rönnblom L
Arthritis Rheumatol 2022 Nov;74(11):1842-1850. Epub 2022 Oct 7 doi: 10.1002/art.42270. PMID: 35729719Free PMC Article
Clinical and Genetic Spectrum of a Large Cohort With Total and Sub-total Complement Deficiencies.
El Sissy C, Rosain J, Vieira-Martins P, Bordereau P, Gruber A, Devriese M, de Pontual L, Taha MK, Fieschi C, Picard C, Frémeaux-Bacchi V
Front Immunol 2019;10:1936. Epub 2019 Aug 8 doi: 10.3389/fimmu.2019.01936. PMID: 31440263Free PMC Article
Complement deficiencies and dysregulation: Pathophysiological consequences, modern analysis, and clinical management.
Schröder-Braunstein J, Kirschfink M
Mol Immunol 2019 Oct;114:299-311. Epub 2019 Aug 14 doi: 10.1016/j.molimm.2019.08.002. PMID: 31421540
Primary immunodeficiency and autoimmunity: lessons from human diseases.
Arason GJ, Jorgensen GH, Ludviksson BR
Scand J Immunol 2010 May;71(5):317-28. doi: 10.1111/j.1365-3083.2010.02386.x. PMID: 20500682
Primary immunodeficiencies associated with pneumococcal disease.
Picard C, Puel A, Bustamante J, Ku CL, Casanova JL
Curr Opin Allergy Clin Immunol 2003 Dec;3(6):451-9. doi: 10.1097/00130832-200312000-00006. PMID: 14612669

Diagnosis

Inherited defects in the complement system.
Leonardi L, La Torre F, Soresina A, Federici S, Cancrini C, Castagnoli R, Cinicola BL, Corrente S, Giardino G, Lougaris V, Volpi S, Marseglia GL, Cardinale F; Immunology Task Force of the Italian Society of Pediatric Allergy and Immunology (SIAIP)
Pediatr Allergy Immunol 2022 Jan;33 Suppl 27(Suppl 27):73-76. doi: 10.1111/pai.13635. PMID: 35080299Free PMC Article
European Society for Immunodeficiencies (ESID) and European Reference Network on Rare Primary Immunodeficiency, Autoinflammatory and Autoimmune Diseases (ERN RITA) Complement Guideline: Deficiencies, Diagnosis, and Management.
Brodszki N, Frazer-Abel A, Grumach AS, Kirschfink M, Litzman J, Perez E, Seppänen MRJ, Sullivan KE, Jolles S
J Clin Immunol 2020 May;40(4):576-591. Epub 2020 Feb 17 doi: 10.1007/s10875-020-00754-1. PMID: 32064578Free PMC Article
Analysis of the Complement System in the Clinical Immunology Laboratory.
Ling M, Murali M
Clin Lab Med 2019 Dec;39(4):579-590. Epub 2019 Oct 3 doi: 10.1016/j.cll.2019.07.006. PMID: 31668271
Complement deficiencies and dysregulation: Pathophysiological consequences, modern analysis, and clinical management.
Schröder-Braunstein J, Kirschfink M
Mol Immunol 2019 Oct;114:299-311. Epub 2019 Aug 14 doi: 10.1016/j.molimm.2019.08.002. PMID: 31421540
Inherited deficiencies of complement and complement-related proteins.
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

Therapy

Multi-component meningococcal serogroup B (MenB)-4C vaccine induces effective opsonophagocytic killing in children with a complement deficiency.
van den Broek B, van Els CACM, Kuipers B, van Aerde K, Henriet SS, de Groot R, de Jonge MI, Langereis JD, van der Flier M
Clin Exp Immunol 2019 Dec;198(3):381-389. Epub 2019 Oct 1 doi: 10.1111/cei.13368. PMID: 31487400Free PMC Article
Invasive meningococcal disease in three siblings with hereditary deficiency of the 8(th) component of complement: evidence for the importance of an early diagnosis.
Dellepiane RM, Dell'Era L, Pavesi P, Macor P, Giordano M, De Maso L, Pietrogrande MC, Cugno M
Orphanet J Rare Dis 2016 May 17;11(1):64. doi: 10.1186/s13023-016-0448-5. PMID: 27183977Free PMC Article
Recombinant human complement component C2 produced in a human cell line restores the classical complement pathway activity in-vitro: an alternative treatment for C2 deficiency diseases.
Martini PG, Cook LC, Alderucci S, Norton AW, Lundberg DM, Fish SM, Langsetmo K, Jönsson G, Lood C, Gullstrand B, Zaleski KJ, Savioli N, Lottherand J, Bedard C, Gill J, Concino MF, Heartlein MW, Truedsson L, Powell JL, Tzianabos AO
BMC Immunol 2010 Aug 20;11:43. doi: 10.1186/1471-2172-11-43. PMID: 20727163Free PMC Article
Rheumatic syndromes associated with complement deficiency.
Barilla-LaBarca ML, Atkinson JP
Curr Opin Rheumatol 2003 Jan;15(1):55-60. doi: 10.1097/00002281-200301000-00010. PMID: 12496511
Hereditary complement (C2) deficiency with dermatomyositis.
Leddy JP, Griggs RC, Klemperer MR, Frank MM
Am J Med 1975 Jan;58(1):83-91. doi: 10.1016/0002-9343(75)90537-9. PMID: 1090155

Prognosis

Primary immunodeficiency association with systemic lupus erythematosus: review of literature and lessons learned by the Rheumatology Division of a tertiary university hospital at São Paulo, Brazil.
Errante PR, Perazzio SF, Frazão JB, da Silva NP, Andrade LE
Rev Bras Reumatol Engl Ed 2016 Jan-Feb;56(1):58-68. Epub 2015 Sep 1 doi: 10.1016/j.rbre.2015.07.006. PMID: 27267335

Clinical prediction guides

Strong Association of Combined Genetic Deficiencies in the Classical Complement Pathway With Risk of Systemic Lupus Erythematosus and Primary Sjögren's Syndrome.
Lundtoft C, Sjöwall C, Rantapää-Dahlqvist S, Bengtsson AA, Jönsen A, Pucholt P, Wu YL, Lundström E, Eloranta ML, Gunnarsson I, Baecklund E, Jonsson R, Hammenfors D, Forsblad-d'Elia H, Eriksson P, Mandl T, Bucher S, Norheim KB, Auglaend Johnsen SJ, Omdal R, Kvarnström M, Wahren-Herlenius M, Truedsson L, Nilsson B, Kozyrev SV, Bianchi M, Lindblad-Toh K; DISSECT consortium, the ImmunoArray consortium, Yu CY, Nordmark G, Sandling JK, Svenungsson E, Leonard D, Rönnblom L
Arthritis Rheumatol 2022 Nov;74(11):1842-1850. Epub 2022 Oct 7 doi: 10.1002/art.42270. PMID: 35729719Free PMC Article
C2 by-pass: Cross-talk between the complement classical and alternative pathways.
Laich A, Patel H, Zarantonello A, Sim RB, Inal JM
Immunobiology 2022 May;227(3):152225. Epub 2022 May 5 doi: 10.1016/j.imbio.2022.152225. PMID: 35567980
Complement and antibody primary immunodeficiency in juvenile systemic lupus erythematosus patients.
Jesus AA, Liphaus BL, Silva CA, Bando SY, Andrade LE, Coutinho A, Carneiro-Sampaio M
Lupus 2011 Oct;20(12):1275-84. Epub 2011 Aug 3 doi: 10.1177/0961203311411598. PMID: 21813590
Primary immunodeficiency and autoimmunity: lessons from human diseases.
Arason GJ, Jorgensen GH, Ludviksson BR
Scand J Immunol 2010 May;71(5):317-28. doi: 10.1111/j.1365-3083.2010.02386.x. PMID: 20500682
Understanding systemic lupus erythematosus physiopathology in the light of primary immunodeficiencies.
Carneiro-Sampaio M, Liphaus BL, Jesus AA, Silva CA, Oliveira JB, Kiss MH
J Clin Immunol 2008 May;28 Suppl 1:S34-41. Epub 2008 Apr 11 doi: 10.1007/s10875-008-9187-2. PMID: 18404362

Recent systematic reviews

Genetic bases of C7 deficiency: systematic review and report of a novel deletion determining functional hemizygosity.
Balduit A, Bianco AM, Mangogna A, Zicari AM, Leonardi L, Cinicola BL, Capponi M, Tommasini A, Agostinis C, d'Adamo AP, Bulla R
Front Immunol 2023;14:1192690. Epub 2023 May 25 doi: 10.3389/fimmu.2023.1192690. PMID: 37304269Free PMC Article

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