Immunoglobulin GM and KM Allotypes in Systemic Lupus erythematosus

Pandey, Janardan P.; Cooper, Glinda S.; Treadwell, Edward L.; Gilkeson, Gary S.; Clair, E. William St.; Dooley, Mary Anne

doi:10.1159/000049190

Cited by 11 publications

(7 citation statements)

References 18 publications

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“…The most simple explanation is the established association between the homozygous presence of G2M(n) and the findings of quantitatively strong Ab responses to polysaccharide Ags (18,19). Several mechanisms have been suggested through which G2M*n and the associated GM*b;f;n haplotype might promote Ab responses, including involvement of haplotype-linked genes and slow processing of Ag by macrophages (17,18,52). Circulating CD27…”

Section: Discussionmentioning

confidence: 99%

Homozygosity for the IgG2 Subclass Allotype G2M(n) Protects against Severe Infection in Hereditary C2 Deficiency

Jönsson

Oxelius

Truedsson

et al. 2006

The Journal of Immunology

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Homozygous C2 deficiency (C2D) is the most common deficiency of the classical complement pathway in Western countries. It is mostly found in patients with autoimmune disease or susceptibility to bacterial infections and in healthy persons. We wished to assess to what extent other immunological factors might explain differences of susceptibility to infections in C2D. For this reason, 44 Swedish patients with C2D were stratified with regard to the severity of documented infections. Investigations of IgG subclass levels, IgG subclass-specific GM allotypes, concentrations of factor B, properdin, and factor H, and polymorphisms of mannan-binding lectin and the Fc receptors FcγRIIa and FcγRIIIb were performed. Homozygosity for the G2M*n allele, which is known to promote Ab responses to polysaccharide Ags, was strongly associated with the absence of severe infections (p < 0.001) in the patients, suggesting a major protective role. The combination of mannan (or mannose)-binding lectin and C2 deficiency was found to be a minor susceptibility factor for invasive infection (p = 0.03). Low concentrations of IgG2 and factor B might sometimes contribute to susceptibility to infection. Other factors investigated did not appear to be important. In conclusion, the findings indicated that efficient Ab responses to polysaccharides are protective against severe infection in C2D. Implications with regard to vaccination should be considered.

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Section: Discussionmentioning

confidence: 99%

Homozygosity for the IgG2 Subclass Allotype G2M(n) Protects against Severe Infection in Hereditary C2 Deficiency

Jönsson

Oxelius

Truedsson

et al. 2006

The Journal of Immunology

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“…Of particular relevance here, GM and KM allotypes influence immune responsiveness to certain autoantigens [22,42], and KIR-MHC class I interactions modify the NK cell cytotoxic activity and NK cell cytokine production profile [43]. Evidence for epistatic contributions of unlinked genes to the risk of autoimmune diseases is accumulating rapidly [44].…”

Section: Discussionmentioning

confidence: 99%

Interaction of KIR Genes and G1M Immunoglobulin Allotypes Confer Susceptibility to Type 2 Diabetes in Puerto Rican Americans

Zúñiga

Romero

Azócar³

et al. 2006

Human Immunology

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“…Using hypothesis driven candidate gene approaches, numerous studies have identified particular GM genes as risk factors for many malignant [9-13], infectious [14-18], and autoimmune diseases [19-24], but most of these findings have not been confirmed or refuted by modern genome-wide association studies (GWAS). One contributing factor might be the absence of GM gene probes in most genotyping platforms.…”

Section: Gm Allotypes and Disease Susceptibilitymentioning

confidence: 99%

The forgotten tale of immunoglobulin allotypes in cancer risk and treatment

Pandey

2013

Exp Hematol Oncol

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Monoclonal antibody (mAb) has fulfilled the promise of being the “Magic Bullet” in oncology with the clinical success of mAbs against CD20, Her-2/neu, epidermal growth factor receptor, vascular endothelial cell growth factor and others in a variety of cancers. Most manufacturers of mouse-human chimeric antibodies (and most immunologists) have treated the constant region of human immunoglobulin (Ig) as if it were naturally monomorphic and therefore not immunogenic in humans. In fact, the constant region of Ig heavy and light chain is highly polymorphic, and yet Ig haplotypes are usually not defined by genome-wide association studies nor are they considered to be important for optimizing mAb therapy. We hereby summarize evidence that Ig allotypes are important and biologically relevant in that they contribute to the etiopathogenesis of many malignant, infectious, and autoimmune diseases. Because Ig allotypes differ from each other in engaging Fc receptor, we argue that future development of effective mAb therapy for cancer should take a patient-specific approach by using the correct allotype for each patient to maximize the efficacy of this therapy.

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Immunoglobulin GM and KM Allotypes in Systemic Lupus erythematosus

Cited by 11 publications

References 18 publications

Homozygosity for the IgG2 Subclass Allotype G2M(n) Protects against Severe Infection in Hereditary C2 Deficiency

Homozygosity for the IgG2 Subclass Allotype G2M(n) Protects against Severe Infection in Hereditary C2 Deficiency

Interaction of KIR Genes and G1M Immunoglobulin Allotypes Confer Susceptibility to Type 2 Diabetes in Puerto Rican Americans

The forgotten tale of immunoglobulin allotypes in cancer risk and treatment

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