| 1. |
- Chen, X., et al.
(författare)
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A genome-wide association study of IgM antibody against phosphorylcholine: shared genetics and phenotypic relationship to chronic lymphocytic leukemia
- 2018
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 27:10, s. 1809-1818
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Tidskriftsartikel (refereegranskat)abstract
- Phosphorylcholine (PC) is an epitope on oxidized low-density lipoprotein (oxLDL), apoptotic cells and several pathogens like Streptococcus pneumoniae. Immunoglobulin M against PC (IgM anti-PC) has the ability to inhibit uptake of oxLDL by macrophages and increase clearance of apoptotic cells. From our genome-wide association studies (GWASs) in four European-ancestry cohorts, six single nucleotide polymorphisms (SNPs) in 11q24.1 were discovered (in 3002 individuals) and replicated (in 646 individuals) to be associated with serum level of IgM anti-PC (the leading SNP rs35923643-G, combined beta = 0.19, 95% confidence interval 0.13-0.24, P = 4.3 x 10-11). The haplotype tagged by rs35923643-G (or its proxy SNP rs735665-A) is also known as the top risk allele for chronic lymphocytic leukemia (CLL), and a main increasing allele for general IgM. By using summary GWAS results of IgM anti-PC and CLL in the polygenic risk score (PRS) analysis, PRS on the basis of IgM anti-PC risk alleles positively associated with CLL risk (explained 0.6% of CLL variance, P = 1.2 x 10-15). Functional prediction suggested that rs35923643-G might impede the binding of Runt-related transcription factor 3, a tumor suppressor playing a central role in the immune regulation of cancers. Contrary to the expectations from the shared genetics between IgM anti-PC and CLL, an inverse relationship at the phenotypic level was found in a nested case-control study (30 CLL cases with 90 age- and sex-matched controls), potentially reflecting reverse causation. The suggested function of the top variant as well as the phenotypic association between IgM anti-PC and CLL risk needs replication and motivates further studies.
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| 2. |
- Caidahl, Kenneth, 1949, et al.
(författare)
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IgM-phosphorylcholine autoantibodies and outcome in acute coronary syndromes.
- 2012
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Ingår i: International Journal of Cardiology. - : Elsevier BV. - 0167-5273 .- 1874-1754. ; 167:2, s. 464-469
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Tidskriftsartikel (refereegranskat)abstract
- Abstract BACKGROUND: Antibodies against proinflammatory phosphorylcholine (anti-PC) seem to be protective and reduce morbidity. We sought to determine whether low levels of immunoglobulin-M (IgM) autoantibodies against PC add prognostic information in acute coronary syndromes (ACS). METHODS: IgM anti-PC titers were measured in serum obtained within 24h of admission from 1185 ACS patients (median age 66years, 30% women). We evaluated major acute cardiovascular events (MACE) and all-cause mortality short- (6months), intermediate- (18months) and long- (72months) terms. RESULTS: Low anti-PC titers were associated with MACE and all-cause mortality at all follow-up times. After adjusting for clinical variables, plasma troponin-I, proBNP and CRP levels, associations remained at all times with MACE, short and intermediate terms also with all-cause mortality. With anti-PC titers below median, adjusted hazard ratios at 18months were for MACE 1.79 (95% confidence interval [CI]: 1.31 to 2.44; p=0.0002) and for all-cause mortality 2.28 (95% CI: 1.32 to 3.92; p=0.003). Anti-PC and plasma CRP were unrelated and added to risk prediction. CONCLUSIONS: Serum IgM anti-PC titers provide prognostic information above traditional risk factors in ACS. The ease of measurement and potential therapeutic perspective indicate that it may be a valuable novel biomarker in ACS.
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