Immune deficiency in abetalipoproteinemia

• May 20th, 2011

Abetalipoproteinemia, caused by mutations in the gene encoding microsomal triglyceride transfer protein, causes fat malabsorption, pigmentary degeneration of the retina, progressive ataxic neuropathy, and acanthocytosis. Many of the features are caused by secondary vitamin E deficiency. It has now been recognized that patients also have immune defects with altered presentation of self and microbial lipid antigens by CD1 molecules, caused by an increased degradation of CD1 molecules (Zeissig et al., 2010, J Clin Invest 120:2889-99).  Calogera M. Simonaro  et al. hypothesized that inflammation was involved in the bone and joint pathology of mucopolysaccharidoses. They bred MPS VII mice with mice deficient in Toll-like receptor 4 (TLR4), and showed decreased bone pathology. This effect was also seen when using the anti-TNF-α drug Remicade (Simonaro et al., 2010, Proc Natl Acad Sci U S A 107:222-7).

Posted by Philippe Campeau, MD

Mevalonate kinase deficiency

• May 10th, 2011

Immune and inflammatory reactions are increasingly being linked to inborn errors of metabolism. It is well known that mevalonate kinase deficiency causes an auto-inflammatory syndrome. It has now been shown that the NALP3 inflammasome, which acts as an intracellular sensor for the innate immunity, is the missing link between a lack of geranylgeranyl pyrophosphate (downstream of mevalonate kinase), and the activation of caspase-1 leading to increases in IL-1β (Pontillo et al., 2010, Eur J Hum Genet 18:844-7).

Posted by Philippe Campeau, MD

New Revised Chapter: 187

• September 20th, 2007

Please review the latest revision to Chapter 187: Immotile Cilia Syndrome (Primary Ciliary Dyskinesia), Including Kartagener Syndrome

by Authors: Bjorn A. Afzelius, Bjorn Mossberg, Sten Erik Bergstrom

Therapeutic gene causing lymphoma

• July 9th, 2006

Nature. 2006 Apr 27;440(7088):1123.
Gene therapy: therapeutic gene causing lymphoma.
Woods NB, Bottero V, Schmidt M, von Kalle C, Verma IM.
3 children who underwent gene therapy for X-linked Severe Combined Immunodeficiency (X-SCID),using therapeutic administration of the IL2RG gene, developped T-cell leukaemia.
In this article, the investigators conducted long term studies in a murine moodel of X-SCID using a similar treatment. One third of the mice developped T-cell lymphomas. This implicates IL2RG in the lymphomagenesis in this model. It underscores the requirement for long-term studies in animals before conducting human gene therapy trials.

For more information on the treatement of genetic disease and on X-SCID, see chapters 5 and 185 of OMMBID, respectively.
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Philippe Campeau, MD
Resident in Medical Genetics at McGill University
OMMBID Blog Administrator