Hereditary Complement Deficiency Diseases

Genetic disorders due to mutations in genes involved in COMPLEMENT SYSTEM PROTEINS. They are often classified into distinct pathway of complement activation where causative mutations are found (e.g., classical pathway, lectin pathway, alternative pathway, and terminal complement pathway).

Also Known As:

Networked: 254 relevant articles (14 outcomes, 13 trials/studies)

Relationship Network

Disease Context: Research Results

Related Diseases

1.	Infections
2.	Autoimmune Diseases (Autoimmune Disease)
3.	Inflammation (Inflammations)
4.	Airway Remodeling
5.	Meningitis

Experts

1.	Truedsson, Lennart: 8 articles (12/2018 - 11/2006)
2.	Garred, Peter: 6 articles (02/2018 - 07/2007)
3.	Skattum, Lillemor: 5 articles (12/2018 - 11/2006)
4.	Kirschfink, Michael: 4 articles (01/2020 - 09/2007)
5.	Frémeaux-Bacchi, Véronique: 4 articles (01/2019 - 12/2003)
6.	Mollnes, Tom Eirik: 4 articles (01/2017 - 09/2007)
7.	Schejbel, Lone: 4 articles (06/2015 - 07/2007)
8.	Truedsson, L: 4 articles (10/2008 - 01/2001)
9.	Genel, Ferah: 3 articles (12/2018 - 11/2006)
10.	Nilsson, Bo: 3 articles (01/2018 - 09/2007)

Drugs and Biologics

Drugs and Important Biological Agents (IBA) related to Hereditary Complement Deficiency Diseases:

1.	Complement System Proteins (Complement)IBA 01/01/1999 - "In both patients, hypocomplementemia with no evidence of congenital complement deficiency or complement consumption persisted even after all other laboratory data and symptoms improved." 01/01/2020 - "Our study shows the potential clinical utility of profiling circulating complement proteins as a comprehensive read-out of various complement deficiencies. " 01/01/2020 - "Here, we applied a novel 'complementomics' approach to study the impact of various complement deficiencies on circulating complement levels. " 01/01/1992 - "Application of molecular biological methods to studies of the complement system and its deficiencies has permitted both the determination of primary structure and chromosomal localization of complement genes (Figure 1) and the capacity to elucidate the molecular basis of complement deficiency disorders." 01/01/1991 - "Studies of inherited complement deficiency states in disease have provided a set of apparent biological facts relating to the protective importance of an intact complement system. "
2.	Antigen-Antibody Complex (Immune Complex)IBA 12/01/2017 - "The first forms identified were inherited complement deficiencies, which predisposed to lupus due to impaired tolerance, and aberrant clearance of apoptotic bodies and immune complexes. " 02/01/1997 - "It is postulated that in this patient defective clearance of antigen-antibody complexes by the reticulo-endothelial system resulted in progressive renal disease as observed in other complement deficiencies. " 12/23/1988 - "The complement deficiencies provide us with a unique opportunity to investigate the origin and development of immune complex excess syndromes." 06/01/1985 - "These observations suggest that the processing of immune complexes in vivo may not be similar in different classical pathway complement deficiency states." 09/06/1984 - "It is also likely that complement deficiency can allow the persistence of low virulence organisms that produce disease solely by an immune complex mechanism. "
3.	Proteins (Proteins, Gene)FDA Link 11/01/2006 - "In epidemiologic or investigative studies addressing the prevalence of complement deficiency, more elaborated diagnostic tests, such as C4 protein allotyping, C2 level measurement and genetic screening for type I C2 deficiency should also be performed." 01/01/1989 - "Genetically determined human complement deficiencies and genetic deficiencies of the corresponding proteins in other species have been recognized for many years. " 08/03/2015 - "Using sera from 16 patients with complement deficiencies and 23 controls, we confirmed that the proteins C1q, C2, C3, C6, C9 and factor H were positively affected by heating, thus the identification of deficient patients was improved when preheating samples. " 01/01/2016 - "This study points out that capillary protein electrophoresis can alert of possible states of low C3, which, once confirmed and common causes ruled out, can lead to CFI and other complement deficiency diagnosis. " 02/01/1998 - "The measurement of C9 deposition alone or in combination with further complement proteins makes this ELISA a valuable tool for assessing the degree and level of complement consumption as well as localizing the missing protein in the case of complement deficiencies."
4.	AntigensIBA 12/01/2003 - "Complete lack of CH50 associated with normal C3 antigen is a strong indication for complement deficiency and should be followed up with further tests to determine which component is missing." 12/01/1985 - "The important contribution of the C2 deficiency is given by the now compelling evidence that it is not the missing individual component itself, but rather the common block in sequential activation of C3 via the classical pathway in both complement deficiencies, that is responsible for the impaired humoral immune response, especially at low antigen doses. " 04/01/1995 - "Probable causative factors include genetic predisposition, complement deficiencies, persistence of antigen, drugs, and environmental factors. " 11/01/2009 - "For example, molecular mimicry, altered apoptosis of the host cells, exposure of as yet masked antigens to the immune system by a given microorganism, and direct viral invasion of immunocompetent cells are all mechanisms that may give rise to dysfunction of the immune system; in addition, some genetically determined deficit of the immune system, such as complement deficiency or deficit of mannose binding lectine, may cause insufficient clearance of infectious agents, whose persistence in the host may determine autoimmunity. " 12/01/1988 - "They all exhibited antibody against the nucleoprotein antigen SSA (Ro), as well as cutaneous involvement, features that have been previously associated with complement deficiency states. "
5.	CytokinesIBA 11/01/2003 - "In addition to evidence of aberrant B and T cell behaviour, lupus is associated with complement deficiencies, and abnormal cytokine function. " 12/01/2007 - "The association between complement deficiencies and SLE could be explained by several mechanisms, including impaired clearance of immune complexes and impaired handling of apoptotic cells, aberrant tolerance induction or changes in cytokine regulation. " 08/01/2002 - "In human lupus, case- control studies have established associations of SLE with certain major histocompatibility class II alleles, complement deficiencies, and polymorphisms of Fc gamma receptor genes, a complement-related gene, and cytokine genes. "
6.	Complement Factor B (Factor B)IBA 07/01/2010 - "In vivo analysis demonstrated that complement deficiency, either C3 or factor B deficiency, resulted in a significant reduction in histological evidence of damage as compared with wild-type control mice (wild type vs C3(-/-), P = 0.02; wild type vs factor B(-/-), P = 0.07; no significant difference between C3(-/-) vs factor B(-/-)). " 06/01/2004 - "To investigate the effect of complement deficiency on atherogenesis and lipidemia, we used mice deficient in the third complement component (C3-/-) or factor B (FB-/-). " 01/01/1995 - "Hemolytic screening tests for complement deficiency were performed and serum concentrations of C1q, C1s, C2, C3, C4, C4 isotypes, factor B, factor D, and properdin were determined. "
7.	Complement Factor H (Factor H)IBA 08/03/2015 - "Using sera from 16 patients with complement deficiencies and 23 controls, we confirmed that the proteins C1q, C2, C3, C6, C9 and factor H were positively affected by heating, thus the identification of deficient patients was improved when preheating samples. " 06/01/2020 - "From the multiple discoveries of monogenic complement deficiencies to the associations of complement factor H and complement factor H-related three polymorphisms to meningococcal disease, the complement pathway is highlighted as being central to the genetic control of meningococcal disease. "
8.	Interferon Type IIBA 11/01/2011 - "Specifically, we discuss a group of conditions, including Aicardi-Goutières syndrome, spondyloenchondrodysplasia, and cases of systemic lupus erythematosus with complement deficiency, in which an upregulation of type I interferons is apparently central to their pathogenesis. " 09/01/2009 - "Secondly, as much emphasized in recent years, poor clearance of apoptotic cells on account of de-fective phagocyte receptors and complement deficiencies involves stimulation of Toll like Receptors (TLRs) 7 and 9 on plasmacytoid dendritic cells (pDCs) and results in release of type I interferon alpha (IFNa). "
9.	Toll-Like Receptors (Toll-Like Receptor)IBA 09/01/2009 - "Secondly, as much emphasized in recent years, poor clearance of apoptotic cells on account of de-fective phagocyte receptors and complement deficiencies involves stimulation of Toll like Receptors (TLRs) 7 and 9 on plasmacytoid dendritic cells (pDCs) and results in release of type I interferon alpha (IFNa). "
10.	Intravenous Immunoglobulins (IVIG)FDA Link 09/08/2020 - "Plasmapheresis ameliorates complement deficiency and removes the offending immune-complexes leading to clinical improvement that was not achieved by IVIG and steroids. "

Therapies and Procedures

1.	Plasmapheresis 09/08/2020 - "Plasmapheresis ameliorates complement deficiency and removes the offending immune-complexes leading to clinical improvement that was not achieved by IVIG and steroids. "
2.	Therapeutics 05/01/1990 - "Complement deficiency and neutrophil dysfunction as risk factors for bacterial infection in newborns and the role of granulocyte transfusion in therapy." 03/01/2023 - "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." 06/14/2019 - "IMD due to capsular group Y predominates in patient with inherited complement deficiency, whilst those on Eculizumab therapy develop IMD due to more diverse capsular groups including non-encapsulated strains." 01/01/2019 - "Results from this large genetic investigation provide evidence of a restricted number of molecular mechanisms leading to complement deficiency and describe the clinical potential adverse events of anti-complement therapy." 07/01/1989 - "Because of the theoretical risk that the infused complement might enhance inflammatory tissue damage, there has been some reluctance to try plasma replacement therapy in SLE patients with complement deficiency. "
3.	Aftercare (After-Treatment) 04/01/2020 - "Such an assessment is based on comprehensive investigations that used mouse models, in vitro studies, and analyses from patients at initiation (basal level to highlight deficiencies) and after treatment initiation (mAb impact on complement), which have further provided key insights into the importance of the complement activation and/or complement deficiencies in mAb activity. "
4.	Splenectomy 10/01/2010 - "Infections of people with complement deficiencies and patients who have undergone splenectomy." 10/01/1989 - "One third or meningitis or meningococcemia happened in correlation with complement deficiency or splenectomy. "
5.	Drug Therapy (Chemotherapy) 08/01/2013 - "Additionally, complement deficiencies may increase the risk of infections and contribute to the higher mortality, especially in patients undergoing aggressive chemotherapy. " 02/28/2014 - "ACIP also recommends vaccination for certain persons at increased risk for Hib disease (i.e., persons who have early component complement deficiencies, immunoglobulin deficiency, anatomic or functional asplenia, or HIV infection; recipients of hematopoietic stem cell transplant; and recipients of chemotherapy or radiation therapy for malignant neoplasms). "