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- Daikeler, Thomas, et al.
(författare)
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Secondary autoimmune diseases occurring after HSCT for an autoimmune disease: a retrospective study of the EBMT Autoimmune Disease Working Party.
- 2011
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Ingår i: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; Aug 11:118(6), s. 1693-8
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Tidskriftsartikel (refereegranskat)abstract
- To specify incidence and risk factors for secondary autoimmune diseases (AD) after HSCT for a primary AD, we retrospectively analysed AD patients treated by HSCT reported to EBMT from 1995 to 2009 with at least one secondary AD (cases) and those without (controls). After autologous HSCT, 29 amongst 347 patients developed at least one secondary AD within 21.9 (0.6-49) months and after allogeneic HSCT, 3 amongst 16 patients. The observed secondary AD included: autoimmune hemolytic anemia (n=3), acquired haemophilia (n=3), autoimmune thrombocytopenia (n=3), antiphospholipid syndrome (n=2), thyroiditis (n=12), blocking TSHR-ab (n=1), Graves' disease (n=2), myasthenia gravis (n=1), rheumatoid arthritis (n=2), sarcoidosis (n=2), vasculitis (n=1), psoriasis (n=1) and psoriatic arthritis (n=1). After autologous HSCT for primary AD, the cumulative incidence of secondary AD was 9.8+/-2 % at 5 years, lupus erythematosus as primary AD and antithymocyte-globulin use plus CD34+ graft selection were important risk factors for secondary AD by multivariate analysis. With a median follow-up of 6.2 (0.54-11) years after autologous HSCT, 26/29 patients with secondary AD were alive, 2 died during their secondary AD (antiphospholipid syndrome, haemophilia) and 1 death was HSCT related. This European multicenter study underlines the need for careful management and follow-up for secondary AD after HSCT.
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| 2. |
- Sawcer, Stephen, et al.
(författare)
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Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis
- 2011
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 476:7359, s. 214-219
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Tidskriftsartikel (refereegranskat)abstract
- Multiple sclerosis is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability. Epidemiological studies have shown that genetic factors are primarily responsible for the substantially increased frequency of the disease seen in the relatives of affected individuals, and systematic attempts to identify linkage in multiplex families have confirmed that variation within the major histocompatibility complex (MHC) exerts the greatest individual effect on risk. Modestly powered genome-wide association studies (GWAS) have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects have a key role in disease susceptibility. Most of the genetic architecture underlying susceptibility to the disease remains to be defined and is anticipated to require the analysis of sample sizes that are beyond the numbers currently available to individual research groups. In a collaborative GWAS involving 9,772 cases of European descent collected by 23 research groups working in 15 different countries, we have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci. Within the MHC we have refined the identity of the HLA-DRB1 risk alleles and confirmed that variation in the HLA-A gene underlies the independent protective effect attributable to the class I region. Immunologically relevant genes are significantly overrepresented among those mapping close to the identified loci and particularly implicate T-helper-cell differentiation in the pathogenesis of multiple sclerosis.
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