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Combined Heterozygo...
Combined Heterozygous Genetic Variations in Complement C2 and C8B : An Explanation for Multidimensional Immune Imbalance?
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- Mannes, Marco (författare)
- Univ Hosp Ulm, Inst Clin & Expt Trauma Immunol, Ulm, Germany.
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- Halbgebauer, Rebecca (författare)
- Univ Hosp Ulm, Inst Clin & Expt Trauma Immunol, Ulm, Germany.
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- Wohlgemuth, Lisa (författare)
- Univ Hosp Ulm, Inst Clin & Expt Trauma Immunol, Ulm, Germany.
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- Messerer, David Alexander Christian (författare)
- Univ Hosp Ulm, Inst Clin & Expt Trauma Immunol, Ulm, Germany.;Friedrich Alexander Univ Erlangen Nurnberg, Univ Hosp Erlangen, Dept Transfus Med & Hemostaseol, Erlangen, Germany.
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- Savukoski, Susa (författare)
- Univ Hosp Ulm, Inst Clin & Expt Trauma Immunol, Ulm, Germany.
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- Schultze, Anke (författare)
- Univ Hosp Ulm, Inst Clin & Expt Trauma Immunol, Ulm, Germany.
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- Berger, Bettina (författare)
- Univ Hosp Ulm, Inst Clin & Expt Trauma Immunol, Ulm, Germany.
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- Knapp, Christiane Leonie (författare)
- Univ Hosp Ulm, Inst Clin & Expt Trauma Immunol, Ulm, Germany.
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- Schmidt, Christoph Q. (författare)
- Ulm Univ, Inst Pharmacol Nat Prod & Clin Pharmacol, Ulm, Germany.
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- Fuerst, Daniel (författare)
- German Red Cross Blood Transfus Serv, Inst Clin Transfus Med & Immunogenet Ulm, Ulm, Germany.;Univ Hosp Ulm, Ulm, Germany.;Ulm Univ, Inst Transfus Med, Ulm, Germany.
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- Hillmer, Morten (författare)
- Ulm Univ, Inst Human Genet, Ulm, Germany.;Ulm Univ, Hosp Ctr, Ulm, Germany.
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- Siebert, Reiner (författare)
- Ulm Univ, Inst Human Genet, Ulm, Germany.;Ulm Univ, Hosp Ctr, Ulm, Germany.
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- Eriksson, Oskar, 1984- (författare)
- Uppsala universitet,Vaskulärbiologi
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- Persson, Barbro (författare)
- Uppsala universitet,Vaskulärbiologi
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- Nilsson, Bo (författare)
- Uppsala universitet,Vaskulärbiologi
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- Nilsson Ekdahl, Kristina (författare)
- Uppsala universitet,Linnéuniversitetet,Institutionen för kemi och biomedicin (KOB),Uppsala University, Sweden,Linnaeus Ctr Biomat Chem, BMC,Vaskulärbiologi,Linnaeus Univ, Linnaeus Ctr Biomat Chem, Kalmar, Sweden
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- Huber-Lang, Markus (författare)
- Univ Hosp Ulm, Inst Clin & Expt Trauma Immunol, Ulm, Germany.
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Univ Hosp Ulm, Inst Clin & Expt Trauma Immunol, Ulm, Germany Univ Hosp Ulm, Inst Clin & Expt Trauma Immunol, Ulm, Germany.;Friedrich Alexander Univ Erlangen Nurnberg, Univ Hosp Erlangen, Dept Transfus Med & Hemostaseol, Erlangen, Germany. (creator_code:org_t)
- 2023-03-01
- 2023
- Engelska.
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Ingår i: Journal of Innate Immunity. - : S. Karger. - 1662-811X .- 1662-8128. ; 15:1, s. 412-427
- Relaterad länk:
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https://doi.org/10.1...
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https://uu.diva-port... (primary) (Raw object)
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https://urn.kb.se/re...
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https://doi.org/10.1...
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https://urn.kb.se/re...
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Abstract
Ämnesord
Stäng
- The complement system plays a crucial role in host defense, homeostasis, and tissue regeneration and bridges the innate and the adaptive immune systems. Although the genetic variants in complement C2 (c.839_849+17del; p.(Met280Asnfs*5)) and C8B (c.1625C>T; p.(Thr542Ile)) are known individually, here, we report on a patient carrying their combination in a heterozygous form. The patient presented with a reduced general condition and suffers from a wide variety of autoimmune diseases. While no autoimmune disease-specific autoantibodies could be detected, genetic analysis revealed abnormalities in the two complement genes C2 and C8B. Therefore, we performed a comprehensive investigation of the innate immune system on a cellular and humoral level to define the functional consequences. We found slightly impaired functionality of neutrophils and monocytes regarding phagocytosis and reactive oxygen species generation and a diminished expression of the C5aR1. An extensive complement analysis revealed a declined activation potential for the alternative and classical pathway. Reconstitution with purified C2 and C8 into patient serum failed to normalize the dysfunction, whereas the addition of C3 improved the hemolytic activity. In clinical transfer, in vitro supplementation of the patient's plasma with FFP as a complement source could fully restore full complement functionality. This study describes for the first time a combined heterozygous genetic variation in complement C2 and C8B which, however, cannot fully explain the overall dysfunctions and calls for further complement deficiency research and corresponding therapies.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Immunologi inom det medicinska området (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Immunology in the medical area (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Medical Genetics (hsv//eng)
Nyckelord
- Genetic complement variants
- Complement imbalance
- Complement reconstitution
- Immunologi
- Immunology
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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Mannes, Marco
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Halbgebauer, Reb ...
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Wohlgemuth, Lisa
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Messerer, David ...
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Savukoski, Susa
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Schultze, Anke
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Berger, Bettina
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Knapp, Christian ...
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Schmidt, Christo ...
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Fuerst, Daniel
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Hillmer, Morten
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Siebert, Reiner
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Eriksson, Oskar, ...
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Persson, Barbro
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Nilsson, Bo
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Nilsson Ekdahl, ...
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Huber-Lang, Mark ...
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Journal of Innat ...
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Linnéuniversitetet
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Uppsala universitet