Genetic factors predicting IFN-gamma generation potential in patients with sarcoidosis and after haematopoietic stem cell transplantation

Our plain-English summary of Genetic factors predicting IFN-gamma generation potential in patients with sarcoidosis and after haematopoietic stem cell transplantation, by A. Lange (International Journal of Immunogenetics, 2008).

The study

• Author: A. Lange
• Journal: International Journal of Immunogenetics
• Published: 2008;35(4-5):385-8
• Cited by: 1 article, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

HLA B8, which is known to associate with a poor proliferative response, constitutes a risk factor of antinuclear antibodies formation in asbestos workers. B8 and DR3 are in a linkage disequilibrium with TNF*A2 allele which characterizes individuals as high TNF-alpha producers. Therefore, haplotype having B8, DR3, TNF*A2 characterizes individuals with rather low proliferative response of lymphocytes and low IFN-gamma generation potential. The above genetical features (B8, DR3 and TNF*A2), associated with a characteristic TNF alpha and IFN gamma generation profile, make sarcoidosis patients prone to develop Lofgren syndrome symptoms. Indeed, low IFN gamma producers genotype (3/3 homozygotes) and HLA DRB1*03 constitute risk factors of Lofgren syndrome in a combined fashion. In patients receiving hematopoietic stem cell transplantation, low IFN gamma producer genotype make people more susceptible to CMV and EBV reactivation as well as to acute and chronic GvHD. Therefore, genetical factors associated with the magnitude of immune response are of a value in predicting the natural history of some diseases thus helping in diagnosis and in tailoring of the treatment.

In plain English

This article was a short review in which the author summarized research by the author's own group in Wroclaw, Poland, on inherited immune-system genes. Most of it described earlier published studies, but some transplant results were cited as still in preparation. On asbestos, the author recalled earlier work finding that factors linked to the gene marker HLA B8 carried a risk of antinuclear antibodies, a type of autoantibody, in workers exposed to asbestos fibres. These antibodies were seen more often in asbestos workers who did not react to certain skin-test antigens, and that lack of reactivity was linked to HLA B8 and/or B7. No fiber type or exposure level was given. Most of the article dealt with sarcoidosis and stem cell transplantation. In earlier work, patients with Lofgren syndrome, a form of sarcoidosis, more often carried a gene type (3/3) linked to low production of interferon-gamma, an immune signalling protein. Among transplant recipients, the 3/3 type was linked with more acute and chronic graft-versus-host disease. In one such unpublished analysis, CMV reactivation occurred in 73% of 3/3 patients versus 31% of others. The author concluded that genes linked to the strength of the immune response may help predict the course of some diseases.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Narrative review, mainly of the author's research group's own earlier published studies, also citing some transplant results described as in preparation
• Who was studied: Studies reviewed covered asbestos workers (earlier Polish studies, numbers not given), sarcoidosis patients with and without Lofgren syndrome, and haematopoietic stem cell transplant recipients at the author's institution in Wroclaw, Poland (a cohort of 110 patients and a group of 84 patients)
• Exposure: Main focus was genetic markers (HLA B8, DR3, TNFA*2 allele, interferon-gamma gene variants). Occupational exposure to asbestos fibres in the earlier asbestos worker studies; no fiber type, product or dose given
• Main results:
  • Earlier work (Matej et al., 1978): factors associated with HLA B8 carried a risk of antinuclear antibody formation in asbestos-exposed workers
  • Earlier work (Lange et al., 1980, 1989): antinuclear antibodies were more frequent in asbestos workers unresponsive to skin-test antigens (PPD and SK-SD), and this lack of reactivity correlated with HLA B8 and/or B7
  • The author interpreted this as asbestos-exposed workers more often being weak in cellular immune response but prone to humoral hyperactivity, including autoantibody formation
  • Earlier work (Wysoczanska et al., 2004): Lofgren syndrome patients more often had DRB1*03 and were more often interferon-gamma 3/3 homozygotes than patients with other forms of sarcoidosis
  • Earlier work (Mlynarczewska et al., 2004): among transplant recipients, those with the low-producer 3/3 genotype more often had acute graft-versus-host disease than those with other genotypes
  • Earlier work (Bogunia-Kubik et al., 2005): the low interferon-gamma producer genotype was also a risk factor for chronic graft-versus-host disease in transplant recipients
  • In 84 consecutively transplanted patients, 35% had CMV reactivation and 25% had EBV reactivation
  • In an analysis cited as in preparation (Jaskula et al.), CMV reactivation occurred in 73% of transplant patients with the 3/3 genotype versus 31% of patients with other genotype combinations
• The authors' conclusion: The author concluded that genetic factors associated with the magnitude of the immune response are of value in predicting the natural history of some diseases, helping in diagnosis and in tailoring treatment

Topics

Medical terms in this study, explained in our Lexicon: STEM.

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