Summary: Advances in basic and clinical immunology in 2007

This summary is based on Advances in basic and clinical immunology in 2007. Journal of Allergy and Clinical Immunology - Volume 122, Issue 1 (July 2008).

Environmental pollutants and the immune system

Exposure to tobacco smoke and other air pollutants induces allergic inflammation in the lung. The basic pro-inflammatory effect could be similar to one observed in pathogenesis of CAD and CVA in patients exposed to tobacco smoke and particulate matter pollutants.

Cross-reactivity to iodinated contrast media

Hypersensitivity to iodinated contrast media agents presents with cross-reactivity and is cell mediated. Skin prick test responses were negative, but patch test results were positive, suggesting participation of cellular mechanisms in these responses.

Related: Allergic (Anaphylactoid) Reaction to Intravenous Contrast


Mind map diagram of adverse reactions to drugs.

The hygiene hypothesis

Decreased atopic sensitization associated with living in a farm was explored by studying bacteria found in cowsheds. Acinetobacter lwoffii and Lactococcus lactis shifted the immune response toward the secretion of TH1 cytokines in a murine model. One begins to wonder if biotherapy with bacterial extracts would be in the future of studies of allergy prevention.


Th1 and Th2 subsets (mind map)

Hereditary angioedema

A follow-up study of the long-term use of stanozolol showed that 21 patients with HAE benefited from stanozolol therapy up to 2 mg daily for more than 25 years. Treatment-related symptoms, predominantly hirsutism, menstrual cycle disorders, and weight gain, developed in 10 patients, but these were easily controlled with dose reduction.

Farkas et al. reported the use of a human C1 inhibitor concentrate therapy for 468 acute attacks in 61 patients with HAE, including 22 children, with efficacy in more than 90% of cases and no reported adverse effects. C1 inhibitor therapy is the best approach from a physiological perspective since it replaces the missing factor. However, the C1 inhibitor has to be administered intravenously which precludes home therapy. Recombinant human C1 inhibitor avoids the infection transmission risks but is difficult to produce.


New therapies for hereditary angioedema (HAE)

Related: Angioedema: A Short Review

Kallikrein inhibitors are effective in reducing HAE symptoms

Angioedema pathogenesis involves the activation of kallikrein to generate bradykinin. A placebo-controlled trial of 48 patients with HAE treated with ecallantide, a kallikrein inhibitor, showed a reduction of HAE attack symptoms in 72% of patients.

A bradykinin type 2 receptor antagonist (Icatibant) has a distinctive advantage over the C1 inhibitor concentrate therapy from the fact that it can be administered subcutaneously. Patients could potentially administer icatibant at home, similar to insulin therapy for diabetes.

Mastocytosis

Systemic mastocytosis is characterized by clonal expansion of mast cells, and most patients present with a genetic mutation in the stem cell factor receptor (KIT) gene. KIT or C-kit receptor is also called CD117. KIT is cytokine receptor expressed on the cell surface. KIT receptors binds to stem cell factors which causes certain types of cells to grow.

Some patients present with eosinophilia and symptoms may overlap with the hypereosinophilic syndrome.

BMT for severe combined immunodeficiency and complete DiGeorge syndrome

Bone marrow transplantation (BMT) for severe combined immunodeficiency and complete DiGeorge syndrome results in long-term survival. Land et al. described 2 patients with complete DiGeorge syndrome who received BMT and were leading normal lives free of frequent infections 18 and 20 years later. BMT could be an alternative to thymus transplantation, for which the number of experts able to perform the procedure is limited.

HIV infection

CD4/CD8 ratio is a sensitive marker to predict HIV infection in infants. Shearer et al. analyzed HIV-exposed infants and found that a CD4/CD8 ratio of 1.8 or less at 3 months of age was more sensitive than CD4+ T-cell counts to predict HIV infection. This finding may be useful to help HIV diagnosis in poorer countries without access to virology laboratories.


Diagram of HIV. Image source: Wikipedia.

References:
Advances in basic and clinical immunology in 2007. Journal of Allergy and Clinical Immunology - Volume 122, Issue 1 (July 2008).
Hereditary angioedema: a decade of human C1-inhibitor concentrate therapy. Farkas et al. J Allergy Clin Immunol 120. 914-917.2007;
Long-term results of bone marrow transplantation in complete DiGeorge syndrome. Land et al. J Allergy Clin Immunol 120. 908-915.2007.
CD4/CD8 ratio predicts infection in HIV infants: the National Heart, Lung and Blood Institute P2C2 study. Shearer et al. J Allergy Clin Immunol 120. 1449-1452.2007.

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