IL-10 -1082 SNP and IL-10 in primary CNS and vitreoretinal lymphomas

Objectives Most primary central nervous system lymphomas (PCNSLs) and primary vitreoretinal lymphomas (PVRLs) are B-cell lymphomas that produce high levels of interleukin (IL)-10, which is linked to rapid disease progression. The IL-10-₁₀₈₂G→A polymorphism (IL-10 SNP) is associated with improved survival in certain non-CNS lymphoma patients. PDCD4 is a tumor suppressor gene and upstream regulator of IL-10. This study examined the correlation between the IL-10 SNP, PDCD4 mRNA expression, and IL-10 expression (at transcript and protein levels) in these lymphoma cells. Materials and methods Single-nucleotide polymorphism (SNP)-typing at IL-10-₁₀₈₂ was performed after microdissecting cytospun PVRL cells from 26 specimens. Vitreal IL-10 and IL-6 levels were measured by ELISA. PCNSL cells from 52 paraffin-embedded sections were microdissected and SNP typed on genomic DNA. RTPCR was performed to analyze expression of IL-10 and PDCD4 mRNA. IL-10- ₁₀₈₂ SNP typing was performed on blood samples of 96 healthy controls. We measured IL-10-₁₀₈₂ SNP expression in 26 PVRLs and 52 PCNSLs and examined its relationship with IL-10 protein and gene expression, respectively. Results More PVRL patients expressed one copy of the IL- 10- ₁₀₈₂G→A SNP with the GA genotype compared to controls. The frequencies of the three genotypes (AA, AG, GG) significantly differed in PVRL versus controls and in PCNSL versus controls. In PVRLs, the vitreal IL-10/IL-6 ratio was higher in IL-10-₁₀₈₂ AG and IL-10-₁₀₈₂ AA patients, compared to IL-10-₁₀₈₂ GG patients. IL-10 mRNA expression was higher in IL-10-₁₀₈₂ AG and IL-10-₁₀₈₂ AA PCNSLs, compared to IL-10-₁₀₈₂ GG PCNSLs. No correlation was found between IL-10 and PDCD4 expression levels in 37 PCNSL samples. Conclusions PVRL and PCNSL patients had similar IL-10-₁₀₈₂ A allele frequencies, but genotype distributions differed from healthy controls. The findings suggest that the IL-10-₁₀₈₂ A allele is a risk factor for higher IL-10 levels in PVRLs and PCNSLs. Higher IL-10 levels have been correlated with more aggressive disease in both PVRLs and PCNSLs, making this finding an important and potentially clinically significant observation.