Human immunoglobulin constant heavy G chain (IGHG) (Fcγ) (GM) genes, defining innate variants of IgG molecules and B cells, have impact on disease and therapy.

TLDR: The role of homozygous IGHG genes with restricted qualities of IgG subclass molecules and B cells is highlighted, which give information about risk/protection, good or bad prognosis, for improvement of clinical care.

About: This article is published in Clinical Immunology.The article was published on 2013-12-01 and is currently open access. It has received 49 citations till now.

Figures

Table 3

Fig. 3C Foreign allelic IgG subclasses in individual patients with PID, treated with IVIG (trough levels, mean of 8 determinations ). Prolonged survival of IgG2*n compared to IgG1*f and IgG1*a (After infusion with IVIG:IgG1*f 20,79 g/l, IgG1*a 10,51 g/l, IgG2*n 5,54 g/l, proportions 4:2:1, given intravenously every 4th week at 400 mg/kg body weight )

Table 1

Table 6 Amino acid substitutions of alternative GM allotypes (allelic IgG subclasses) Ref. 24

Table 5 Reference levels (g/l) of allotypic (allelic) IgG subclasses (Mean, SD) in 6 common IGHG diplotypes from healthy adults Ref 9.

Table 4

Frequently asked questions

Q1. What are the contributions in this paper?

The IGHG allele ( allotypes ), expressed in homozygous or heterozygous forms, are assessed by new serological methods this paper. 

Q2. What is the function of IGHG (Fc) (GM) genes?

The function of IGHG (Fc) (GM) genes results in different susceptibility/resistenceto bacterial infections and to viral discrimination. 

Q3. What are the main effects of IGHG genes?

IGHG genes have direct active effects as in infections, immunodeficiency, allergy, autoimmunity and malignancy, but have also modifying effects in monogenic diseases. 

Q4. What is the effect of IgG on pathogenesis?

Both low levels and restricted qualities of IgG antibodies (Fc domains) expressed from different B cells have influence on pathogenesis. 

Q5. What is the thymic-dependent type of immunogen?

The conventional Haemophilus polysaccharide is thought to be the thymic-independent type of immunogen, whereas the protein-conjugated vaccine is thymicdependent. 

Q6. What is the effect of the IGHG1 gene on the HCMV?

HCMVTRL11/IRL11 encoded FcR has increased binding to IGHG1*f compared to IGHG1*a,P=0.0005, with potential implications for genetic etiology of HCMV associated diseases [26]. 

Q7. How many batches of IgG were investigated for different subclasses?

7 commercial IVIG preparation, mean of five batches, respectively, were investigated for allelic IgG subclasses compared to a normal serum pool (2000 sera). 

Q8. What is the common method of assessing IgG subclasses?

Both IGHG gene mapping and quantities of allelic IgG subclasses are assessed by a sensitive competitive ELISA [4-6], at individual and population levels. 

Q9. What is the possibility of tracing foreign IgG subclasses?

In passive immunotherapy with humanized (IgG1) mouse monoclonals, the foreign allelic IgG subclasses could be traced and half-life times registrated. 

Q10. What is the nature of the interactions between rare and common variants?

The nature and extent of interactions between rare and common gene variants is currently unknown, but common variants may act as “modifier” genes that affect the clinical penetrance of rare variants analogous to the genetic model as described in monogenic conditions as WAS and AT. 

Q11. What is the significance of the results of a simultaneous genotyping of GM and Fc?

Simultaneous genotyping of GM and Fc could significantlyimprove their ability to predict a patient´s prognosis of non-small cell lung cancer. 

Q12. What is the role of IGHG in the immune system?

Identification of the causative IGHG alleles, their functional conseqencies and biological mechanisms have already yielded important insight into the immune system by which they influence disease pathogenesis. 

Q13. How many Dutch colonists survived typhoid and yellow fever?

Descendants of 367 Dutch colonists (100 families) who emigrated to Surinam in 1847, survived epidemics of typhoid and yellow fever with a total morality of 60%. 

Q14. What are the distinguished alternative IGHG(GM) allotypes?

The distinguished alternative IGHG(GM) allotypes (alleles) are expressed as homozygous or heterozygous IGHG genes constituting the IgG subclass gene. 

Q15. What is the common IGHG diplotype in children with asthma?

Children with bronchial asthma but with IgE levels < 10 kU/l are instead associated with the opposite IGHG*ga-n/*ga-n diplotype, infection proneness and IgG subclass deficiencies [34].