Reports of abnormal cervical cancer screening tests in systemic sclerosis.

OBJECTIVE: To assess the prevalence of abnormal cervical cancer screening (Pap tests) reported by women with SSc onset before the age of 50 yrs. METHODS: Female members of a Canadian multi-centre SSc cohort completed standardized assessments and were questioned regarding a history of an abnormal Pap test. Potential correlates examined included demographics, reproductive history, smoking, diffuse vs limited SSc type, immunosuppressant exposure and SSc duration. RESULTS: In the 320 women with SSc onset before the age of 50 yrs, the life-time prevalence of an abnormal Pap test (according to self-report) was 25.4% (95% CI CI 20.9, 30.4%). By comparison, self-reported prevalence of abnormal Pap tests among general population Canadian females was recently reported at 13.8% (95% CI 11.6, 16.4%). Women with diffuse SSc (n = 142), tended to have a higher prevalence of self-reported cervical dysplasia (31.7%) compared with those with limited disease (20.7%), but the CIs overlapped. A multivariate logistic regression found a significant positive association between self-reported abnormal Pap test and diffuse disease [odds ratio (OR) 1.87; 95% CI 1.01, 3.47]. An independent association of an abnormal Pap test with smoking (OR 2.43; 95% CI 1.23, 4.78) and with younger age at disease onset was also noted. CONCLUSIONS: We noted a high prevalence of abnormal Pap tests self-reported in our sample. Increased risk was seen among those with diffuse SSc, and also among smokers and those with a younger age at disease onset. Thus, it seems prudent to ensure that adequate attention is paid to cervical cancer screening for women with SSc.

Neuroendocrine host factors and inflammatory disease susceptibility.

The etiology of autoimmune diseases is multifactorial, resulting from a combination of genetically predetermined host characteristics and environmental exposures. As the term autoimmune implies, immune dysfunction and dysregulated self-tolerance are key elements in the pathophysiology of all these diseases. The neuroendocrine and sympathetic nervous systems are increasingly recognized as modulators of the immune response at the levels of both early inflammation and specific immunity. As such, alterations in their response represent a potential mechanism by which pathologic autoimmunity may develop. Animal models of autoimmune diseases show pre-existing changes in neuroendocrine responses to a variety of stimuli, and both animal and human studies have shown altered stress responses in the setting of active immune activation. The potential role of the neuroendocrine system in linking environmental exposures and autoimmune diseases is 2-fold. First, it may represent a direct target for toxic compounds. Second, its inadequate function may result in the inappropriate response of the immune system to an environmental agent with immunogenic properties. This article reviews the relationship between autoimmune diseases and the neuroendocrine system and discusses the difficulties and pitfalls of investigating a physiologic response that is sensitive to such a multiplicity of environmental exposures.

A new antibody in rheumatoid arthritis targeting glycated IgG: IgM anti-IgG-AGE.

Hyperglycaemia and/or oxidative stress can cause IgG to be modified by advanced glycation end products (AGE). Three patients with aggressive rheumatoid arthritis (RA) and vasculitis are described who have high titres of IgM antibodies against AGE-modified IgG (IgM anti-IgG-AGE). Diabetics and randomly selected patients with rheumatic diseases, including 50 additional RA patients, were tested for IgM and IgA anti-IgG-AGE by ELISA. AGE-modified proteins were detected using the nitroblue tetrazolium (NBT) colorimetric method. The presence of Nepsilon (carboxymethyl) lysine, an AGE modification, was detected on IgG-AGE by immunoblotting. A total of 20/41 (49%) rheumatoid factor (RF)-positive RA patients tested had IgM anti-IgG-AGE antibodies, 4/12 (33%) RF-positive systemic lupus erythematosus (SLE) patients, 3/5 RF-positive patients with primary Sjogren's syndrome (SS), and 3/5 RF-positive diabetics. All patients with RF-negative RA, SLE, SS, osteoarthritis (24), spondyloarthritis (15), adult-onset Still's disease (8), diabetes (25) and healthy controls (20) were anti-IgG-AGE negative. RF and IgM anti-IgG-AGE appeared to be a linked response. The IgM anti-IgG-AGE, along with IgG-AGE, may contribute to the pathogenesis of RA.

X-linked nephrogenic diabetes insipidus: from the ship Hopewell to RFLP studies.

Nephrogenic diabetes insipidus (NDI; designated 304800 in Mendelian Inheritance in Man) is an X-linked disorder with abnormal renal and extrarenal V2 vasopressin receptor responses. The mutant gene has been mapped to Xq28 by analysis of RFLPs, and tight linkage between DXS52 and NDI has been reported. In 1969, Bode and Crawford proposed, under the term "the Hopewell hypothesis," that most cases in North America could be traced to descendants of Ulster Scots who arrived in Nova Scotia in 1761 on the ship Hopewell. They also suggested a link between this family and a large Mormon pedigree. DNA samples obtained from 13 independent affected families, including 42 members of the Hopewell and Mormon pedigrees, were analyzed with probes in the Xq28 region. Genealogical reconstructions were performed. Linkage between NDI and DXS304 (probe U6:2.spl), DXS305 (St35-691), DXS52 (St14-1), DXS15 (DX13), and F8C (F814) showed no recombination in 12 families, with a maximum lod score of 13.5 for DXS52. A recombinant between NDI and DXS304, DXS305, was identified in one family. The haplotype segregating with the disease in the Hopewell pedigree was not shared by other North American families. PCR analysis of the St14 VNTR allowed the distinction of two alleles that were not distinguishable by Southern analysis. Carrier status was predicted in 24 of 26 at-risk females. The Hopewell hypothesis cannot explain the origin of NDI in many of the North American families, since they have no apparent relationship with the Hopewell early settlers, either by haplotype or by genealogical analysis. We confirm the locus homogeneity of the disease by linkage analysis in ethnically diverse families. PCR analysis of the DXS52 VNTR in NDI families is very useful for carrier testing and presymptomatic diagnosis, which can prevent the first manifestations of dehydration.