Homozygous C2 Deficiency: Association with Defective Alternative Pathway Function and Immunoglobulin Deficiency

Sanal, Özden; L, Yel; Tezcan, İlhan; Ersoy, Figen; Ai, Berkel

doi:10.1159/000237287

Cited by 8 publications

(13 citation statements)

References 14 publications

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“…Although IgG subclass levels were normal, specific IgG responses to immunization against S. pneumoniae and H. influenzae were significantly impaired. In another report, of five patients with homozygous type I C2 deficiency (caused by a 28-bp deletion in the C2 gene) in two families, three suffered from recurrent infections (387). These patients had additional risk factors; two patients (one from each family) had IgG2 deficiency or IgA deficiency.…”

Section: Inherited Deficiencies Of Complement Activationmentioning

confidence: 97%

Infections of People with Complement Deficiencies and Patients Who Have Undergone Splenectomy

2010

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SUMMARY The complement system comprises several fluid-phase and membrane-associated proteins. Under physiological conditions, activation of the fluid-phase components of complement is maintained under tight control and complement activation occurs primarily on surfaces recognized as “nonself” in an attempt to minimize damage to bystander host cells. Membrane complement components act to limit complement activation on host cells or to facilitate uptake of antigens or microbes “tagged” with complement fragments. While this review focuses on the role of complement in infectious diseases, work over the past couple of decades has defined several important functions of complement distinct from that of combating infections. Activation of complement in the fluid phase can occur through the classical, lectin, or alternative pathway. Deficiencies of components of the classical pathway lead to the development of autoimmune disorders and predispose individuals to recurrent respiratory infections and infections caused by encapsulated organisms, including Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae. While no individual with complete mannan-binding lectin (MBL) deficiency has been identified, low MBL levels have been linked to predisposition to, or severity of, several diseases. It appears that MBL may play an important role in children, who have a relatively immature adaptive immune response. C3 is the point at which all complement pathways converge, and complete deficiency of C3 invariably leads to severe infections, including those caused by meningococci and pneumococci. Deficiencies of the alternative and terminal complement pathways result in an almost exclusive predisposition to invasive meningococcal disease. The spleen plays an important role in antigen processing and the production of antibodies. Splenic macrophages are critical in clearing opsonized encapsulated bacteria (such as pneumococci, meningococci, and Escherichia coli) and intraerythrocytic parasites such as those causing malaria and babesiosis, which explains the fulminant nature of these infections in persons with anatomic or functional asplenia. Paramount to the management of patients with complement deficiencies and asplenia is educating patients about their predisposition to infection and the importance of preventive immunizations and seeking prompt medical attention.

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Section: Inherited Deficiencies Of Complement Activationmentioning

confidence: 97%

Infections of People with Complement Deficiencies and Patients Who Have Undergone Splenectomy

2010

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“…It is proposed that impaired MBL-mediated immunity in CVID patients leads to recurrent infections at an earlier age [28]. There are several reports on the role of complement deficiencies in CVID patients, while the possible contribution of defects in the classical and alternative pathways has been uncertain [34,35].…”

Section: Discussionmentioning

confidence: 99%

“…Dysregulation in this system could be associated with both increased susceptibility to infections and autoimmune diseases [23][24][25]. Some documented studies [26][27][28][29][30][31][32][33][34][35][36][37][38] showed that dysregulation of MBL pathway, caused structural mutations of the MBL2 gene [26] and three different structural variants, including B, C, D and the promoter haplotypes HY (high producing), LY (intermediate) and LX (low producing) have the most important effects on serum MBL concentration. MBL variants and polymorphisms [27,28], is associated with an increased frequency of severe respiratory tract infections, autoimmunity and earlier onset age of disease in CVID.…”

Section: Introductionmentioning

confidence: 99%

Mannose-binding lectin polymorphisms in common variable immunodeficiency

et al. 2009

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Common variable immunodeficiency (CVID) is a heterogeneous group of disorders, characterized by hypogammaglobulinemia and increased susceptibility to infections, autoimmunity and malignancies. This study was performed to analyze the Mannose-binding lectin (MBL) polymorphisms in Iranian patients with CVID. Thirty-five CVID patients who were treated at Children's Medical Center and 100 matched controls were enrolled in this study. Sixth single-nucleotide polymorphisms of the MBL gene were analyzed using PCR-SSP method. Comparison of MBL exon 1 coding alleles between patients and controls revealed that A allele (wild-type) was significantly decreased in CVID group, whereas B allele was overrepresented in the patient group. High frequency of heterozygous (A/O) in the patient group and high frequency of homozygous for wild-type coding regions in the control group were detected. Comparison of MBL haplotype promoters between CVID patients and controls showed that LYPB haplotype was significantly overrepresented in the CVID group. Mutant and low-producing MBL alleles and haplotypes might reflect as an associated genetic factor in CVID patients, which could play as a susceptibility factor in CVID.

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“…1, the causes were serious: pneumococcal meningitis and later arthritis with septicaemia. Most reports of patients with C2 deficiency indicate that severe/recurrent infections started in infancy or childhood, 3,8−14 but seldom was the onset of symptoms so early 3,14−19 . The presenting manifestation in those cases was predominately either meningitis 14,17−19 or soft tissue infections 3,16 .…”

Section: Discussionmentioning

confidence: 99%

Early manifestation and recognition of C2 complement deficiency in the form of pyogenic infection in infancy

Litzman

Freiberger

Bartoňková

et al. 2003

J Paediatrics Child Health

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Homozygous C2 Deficiency: Association with Defective Alternative Pathway Function and Immunoglobulin Deficiency

Cited by 8 publications

References 14 publications

Infections of People with Complement Deficiencies and Patients Who Have Undergone Splenectomy

Infections of People with Complement Deficiencies and Patients Who Have Undergone Splenectomy

Mannose-binding lectin polymorphisms in common variable immunodeficiency

Early manifestation and recognition of C2 complement deficiency in the form of pyogenic infection in infancy

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