Combining MYD88 L265P mutation detection and clonality determination on CSF cellular and cell-free DNA improves diagnosis of primary CNS lymphoma.

Diagnosis of primary central nervous system lymphoma (PCNSL) is challenging, and although brain biopsy remains the gold standard, cerebrospinal fluid (CSF) constitutes a less invasive source of lymphomatous biomarkers. In a retrospective cohort of 54 PCNSL cases tested at diagnosis or relapse, we evaluated the contribution of immunoglobulin heavy chain (IGH) gene clonality and MYD88 L265P detection on both CSF cell pellets and supernatants, in comparison with cytology, flow cytometry, interleukin (IL)-10 and IL-6 quantification. Clonality assessment included a new assay to detect partial IGH-DJ rearrangements. Clonal IGH rearrangements and/or MYD88 L265P mutation were detected in 27 (50%) cell pellets and 24 (44%) supernatant cell-free (cf) DNA. Combining analyses on both compartments, 36 (66%) cases had at least one detectable molecular marker, present only in cfDNA for 9 (16%) of them. While cytology and flow cytometry were positive in only 7 (13.0%) and 9 (17.3%) cases respectively, high IL-10 levels were observed in 36 (66.7%) cases. Overall, taking into account molecular and cytokine results, 46/54 (85%) cases had at least one lymphomatous biomarker detectable in the CSF. These results show that this combination of biomarkers evaluated on both cell pellet and supernatant CSF fractions improves significantly the biological diagnosis of PCNSL.

Glutathione S-transferases related to P. aeruginosa lung infection in cystic fibrosis children: preliminary study.

OBJECTIVES: In cystic fibrosis (CF) children, we investigated the predictive impact of glutathione S-transferases (GST) activity and genotypes P1, M1 and T1, and antioxidant levels on stage-severity of Pseudomonas aeruginosa lung infection. METHODS: GST activity was determined in whole blood by spectrophotometry, and GST genotypes by multiplex PCR RFLP for 36 CF and 9 control children. Levels of glutathione in erythrocyte and vitamins A, E and C in plasma were measured by HPLC. RESULTS: No difference in GST activity and no relationship between GST activity and antioxidant levels were observed in CF children as compared to controls. However, GST activity was lower in CF children with severe clinical status and infection, and the frequency of GSTP1 wild type genotype AA, prevalent in uninfected CF children (75%), decreased in infected ones (33%). CONCLUSION: GST activity and genotype could play an important role in modulating P. aeruginosa lung infection in CF patients.