CASPASE-12, Rheumatoid Arthritis, and the Dog That Didn’t Bark

CASPASE-12 (CASP12) has an anti-inflammatory function during infection. To determine and if CASP12 could protect against inflammatory disease, we investigated the distribution of CASP12 alleles in African-Americans (AA) with rheumatoid arthritis (RA). CASP12 homozygous patients had lower baseline joint narrowing and total disease scores. However, there was no significant difference for distribution of CASP12 genotypes between AA controls and patients with RA, or any other clinical criteria for this disease. CASP12 homozygosity appears to be, at best a subtle protective factor for some aspects of RA in AA patients. This raises an intriguing issue as to how this protein would not have a more significant role in an inflammatory disease process

CASPASE-12 and Lupus: The Curious Case of the Dog That Didn’t Bark

CASPASE-12 (CASP12) has an anti-inflammatory function during infection, and is a risk factor for sepsis in African-Americans (AA). To determine if CASP12 could be protective for systemic lupus erythematosus (SLE) in AA, we genotyped AA SLE patients and controls. We found that, at best, there was a weak association between CASP12 genotype with the absence of anti-dsDNA autoantibodies in SLE patients. No effect was seen upon serum interleukin-1 beta levels, nor was any other protective effect noted for the CASP12 genotype, whether upon association with SLE, or any of the 11 American College of Rheumatology classification criteria. We concluded that CASP12 genotype thus does not influence the phenotype of SLE in AA. This raises the issue as to why this protein would not play a more significant role in a chronic inflammatory disease process

CASPASE-12 and Rheumatoid Arthritis in African-Americans

CASPASE-12 (CASP12) has a downregulatory function during infection and thus may protect against inflammatory disease. We investigated the distribution of CASP12 alleles (#rs497116) in African-Americans (AA) with rheumatoid arthritis (RA). CASP12 alleles were genotyped in 953 RA patients and 342 controls. Statistical analyses comparing genotype groups were performed using Kruskal–Wallis non-parametric ANOVA with Mann–Whitney U tests and chi-square tests. There was no significant difference in the overall distribution of CASP12 genotypes within AA with RA, but CASP12 homozygous patients had lower baseline joint-narrowing scores. CASP12 homozygosity appears to be a subtle protective factor for some aspects of RA in AA patients

Design, synthesis, and evaluation of indole compounds as novel inhibitors targeting Gp41

A series of indole ring containing compounds were designed based on the structure of the gp41 complex in the region of the hydrophobic pocket. These compounds were synthesized using a Suzuki Coupling reaction, and evaluated using a fluorescence binding assay and cell-cell fusion assay. The observed inhibition constant of compound 7 was 2.1µM, and the IC(50) for cell-cell fusion inhibition was 1.1µM. Assay data indicated that 7 is a promising lead compound for optimization into an effective low molecular weight fusion inhibitor