Association of atopy and eczema with polymorphisms in T-cell immunoglobulin domain and mucin domain—IL-2–inducible T-cell kinase gene cluster in chromosome 5q33

2011-01-26T03:55:00.000-08:00

Background

The T-cell immunoglobulin domain and mucin domain (TIM) gene family and the gene for IL-2–inducible T-cell kinase (ITK), located in chromosome 5q33 and potentially involved in the T-cell proliferation and differentiation, are good candidate genes for allergic diseases.

Objective

We assessed the role of polymorphisms in the TIM family genes and ITK in atopy, eczema, and asthma.

Methods

Twenty-one polymorphisms in the TIM-ITK gene cluster were genotyped in 564 children enrolled in the Tucson Children's Respiratory Study. Skin prick tests to common allergens were performed at age 6.1 years (n=508), age 10.8 years (n=539), and age 16.6 years (n=424). Asthma and eczema were assessed by questionnaire at these 3 points. Averaged relative risks were estimated.

Results

One 15-bp insertion/deletion in exon 4 of TIM1 was significantly related to atopy and eczema (relative risk associated with carrying at least 1 rare allele=1.24 [1.07-1.45], P=.005; and 1.43 [1.01-2.01], P=.004, respectively). The 3 tested single nucleotide polymorphisms (SNPs) in TIM3 were significantly related to atopy and eczema. One of them, at position +4259 calculated from the translation start site, predicts a putative change in the amino acid sequence of the protein, and was the most strongly related to atopy (relative risk=1.28 [1.12-1.47]; P=.0003). SNPs in the 5′ genomic region in ITK, which show moderate linkage disequilibrium with those in TIM3, had an independent effect on atopy. None of the polymorphisms studied was related to asthma.

Conclusion

Our findings support a potential role for SNPs in TIM1, TIM3, and ITK, independent of each other, in allergic diseases.

Infection outcomes in patients with common variable immunodeficiency disorders: Relationship to immunoglobulin therapy over 22 years

2011-01-26T03:41:00.000-08:00

Background
Common variable immunodeficiency disorders (CVIDs) are the most common forms of symptomatic primary antibody failure in adults and children. Replacement immunoglobulin is the standard treatment, although there are few consistent data on optimal dosages and target trough IgG levels required for infection prevention.

Objective

To provide data to support the hypothesis that each patient requires an individual dose of therapeutic immunoglobulin to prevent breakthrough infections and that efficacious trough IgG levels vary between patients.

Methods

Data, collected prospectively from a cohort of 90 patients with confirmed CVIDs from 1 center over a follow-up period of 22 years, was validated and analyzed. Immunoglobulin doses had been adjusted in accordance with infections rather than to achieve a particular trough IgG level. Doses to achieve infection-free periods were determined and resultant trough levels analyzed. A smaller group of patients with X-linked agammaglobulinemia was analyzed for comparison.

Results

Patients with a CVID had a range of trough IgG levels that prevented breakthrough bacterial infections (5-17 g/L); viral and fungal infections were rare. Doses of replacement immunoglobulin to prevent breakthrough infections ranged from 0.2 to 1.2 g/kg/mo. Those with proven bronchiectasis or particular clinical phenotypes required higher replacement doses. Patients with X-linked agammaglobulinemia showed a similar range of IgG levels to stay infection-free (8-13 g/L).

Conclusion

These data offer guidance regarding optimal doses and target trough IgG levels in individual patients with CVIDs with or without bronchiectasis and for particular clinical phenotypes. The goal of replacement therapy should be to improve clinical outcome and not to reach a particular IgG trough level.

medical-journals.

Association of atopy and eczema with polymorphisms in T-cell immunoglobulin domain and mucin domain—IL-2–inducible T-cell kinase gene cluster in chromosome 5q33

Background

Objective

Methods

Results

Conclusion

Infection outcomes in patients with common variable immunodeficiency disorders: Relationship to immunoglobulin therapy over 22 years

Objective

Methods

Results

Conclusion