Leukocytes infiltrating the pancreatic islets of nonobese diabetic mice are transformed into inactive exiles by combinational anti-cell adhesion therapy.

Leukocytes infiltrate the pancreatic islets of nonobese diabetic mice, causing beta-cell destruction and autoimmune Type I diabetes. Here, we completely blocked adoptive transfer of diabetes and reduced spontaneous disease incidence from 71% to 17% by simultaneously administering a combination of antibodies directed against alpha4, beta2, and beta7 integrins and their ligands VCAM-1, MAdCAM-1, and ICAM-1 for 52 and 28 days, respectively. CD4 and CD8 T cells and macrophages were excluded from islets and remained entrapped in a peri-islet location as inactive exiles, no longer expressing normal levels of interferon-gamma, interleukin-4, and iNOS. Only IL-10 expression was retained, which could aid immunosuppression. Infiltrating leukocytes retained a peri-islet location, even 215 days following suspension of antibody treatment, potentially forming a barrier to the entry of active, autoantigen-reactive T cells. Combination treatment was effective against spontaneous disease when administered from 7 days of age but ineffective when initiated late in the prediabetic period (day 40 or 70). Nevertheless, anti-alpha4 subunit mAb monotherapy alone was very effective, reducing insulitis to levels similar to those obtained with combinational antibody treatment, suggesting that alpha4 integrins are major receptors contributing to leukocyte infiltration. Treatment with anti-alpha4 integrin antibody retained some therapeutic benefit when administered from days 7, 40, or 70 of age. The results have implications for the treatment of diabetes and provide a unique insight into the fate of disease-forming leukocytes following anti-CAM therapy.

Hepatitis C antibodies in haemodialysis and pattern of end-stage renal failure in Gassim, Saudi Arabia.

As by the end of 1992, 96 (47 females; 49 females) patients were on regular dialysis treatment for end stage renal failure (ESRF) in 5 haemodialysis HD units, the Gassim region of Saudi Arabia. Because of lack of facilities, paediatric patients were under-represented, age range being 11 to 80 years. Systemic hypertension (47%), followed by hereditary/congenital conditions (23%) and non-insulin dependent diabetes mellitus NIDDM (19%) were the most common causes of ESRF in the region. One patients developed ESRF 14 years after donor nephrectomy. Overall prevalence of HCAb was 50% with a range of 17.24% to 83%. Based, especially, on the findings in two of the units which between them handle 57% (55/96) of the patients, we believe that the practice of machine isolation policy (MIP) rather than blood transfusion is largely responsible for this wide variation in prevalence between the centres. Considering the very high overall prevalence of the Kingdom, we suggest the MIP should no longer be optional and should be part of the universal infection precautions for HD patients. Comparing Gassim with findings from Taif, there may be some variation in the pattern of ESRF between different parts of the Kingdom. More reports will be needed to document this. Donor nephrectomy as a cause of ESRF is being recorded for the first time in the Kingdom. Vigilance is important. Similarly, we believe that sexual intercourse as a probable route of hepatitis C virus HCV transmission is being recorded for the first time in the Kingdom.