A comparison of serologic reactivity among SLE patients with or without anti-Ro (SS-A) antibodies

The serum from 112 patients with systemic lupus erythematosus (SLE) was examined to compare serologic reactivity among anti-Ro positive and anti-Ro negative patients. While hypergammaglobulinemia, rheumatoid factor (RF) and elevated Clq binding were significantly more frequent among the anti-Ro positive group there was no increase in the frequency of anti-dsDNA antibody measured by the Farr assay or antibodies to ssDNA, dsDNA, poly dG ̇ poly dC, poly (dA-dT) and cardiolipin measured by ELISA. Patients with the highest levels of anti-DNA antibody by the Farr assay did not have any increased frequency of anti-Ro antibodies. We concluded that anti-RO and anti-DNA antibodies are independently regulated. The frequent occurrence of RF in anti-Ro positive SLE patients may provide a useful screening assay for this autoantibody among pregnant SLE patients

Family history characteristics, tumor microsatellite instability and germline MSH2 and MLH1 mutations in hereditary colorectal cancer

Recent characterization of the molecular genetic basis of hereditary nonpolyposis colorectal cancer provides an important opportunity for identification of individuals and their families with germline mutations in mismatch repair genes. Cancer family history criteria that accurately define hereditary colorectal cancer are necessary for cost-effective testing for germline mutations in mismatch repair genes. The present report describes the results of analysis of 33 colorectal cancer cases/families that satisfy our modified family history criteria (Mount Sinai criteria) for colorectal cancer. Fourteen of these families met the more stringent Amsterdam criteria. Germline MSH2 and MLH1 mutations were identified by the reverse transcription-polymerase chain reaction and the protein truncation test, and confirmed by sequencing. Microsatellite instability analysis was performed on available tumors from affected patients. MSH2 or MLH1 mutations were detected in 8 of 14 Amsterdam criteria families and in 5 of the remaining 19 cases/families that only satisfied the Mount Sinai criteria. Three of the latter families had features of the Muir-Torre syndrome. A high level of microsatellite instability (MSI-H) was detected in almost all (16/18) colorectal cancers from individuals with MSH2 and MLH1 mutations, and infrequently (1/21) in colorectal cancer specimens from cases without detectable mutations. Families with germline MSH2 and MLH1 mutations tended to have individuals affected at younger ages and with multiple tumors. The Amsterdam criteria are useful, but not sufficient, for detecting hereditary colorectal cancer families with germline MSH2 and MLH1 mutations, since a proportion of cases and families with mutations in mismatch repair genes will be missed. Further development of cancer family history criteria are needed, using unbiased prospectively collected cases, to define more accurately those who will benefit from MSH2 and MLH1 mutation analysis