Autoimmunity as an aetiological factor in vitiligo

Vitiligo is a common dermatological disorder characterized by the presence on the skin of depigmented macules resulting from the destruction of cutaneous melanocytes. Autoimmunity is an important hypothesis with regard to vitiligo aetiology and the evidence for autoimmune responses being involved in the pathogenesis of this disorder will be discussed in the present review. All immune system compartments, including innate and adaptive immunity have been implicated in vitiligo development. Particularly relevant are autoantibodies and autoreactive T cells in vitiligo patients that have cytotoxic effects upon pigment cells. Furthermore, predisposition to vitiligo appears to be associated with certain alleles of the major histocompatibility complex class II antigens as well as with other autoimmune-susceptibility genes. Moreover, the association of vitiligo with autoimmune disorders, the animal models of the disease, and the positive response to immunosuppressive therapeutic agents emphasize the role of autoimmunity in the development of this disorder.     

The changing clinical pattern of Reye's syndrome 1982-1990

OBJECTIVE: To describe trends in the clinical pattern of Reye's syndrome in the British Isles between 1982 and 1990; and to determine the relation between any changes and the June 1986 warnings against the use of aspirin in children. DESIGN: Development, and application to reported cases, of a scoring system designed such that patients showing the typical clinical and pathological features of 'classical' Reye's syndrome scored highly. The relations between 'Reye scores' and a number of explanatory variables were explored using multivariable analysis. SETTING: British Isles. SUBJECTS: 445 cases fulfilling the Reye's syndrome case definition reported to the surveillance scheme between January 1982 and December 1990. MAIN OUTCOME MEASURE: Individual 'Reye score'. RESULTS: Cases with high scores were more likely to have occurred in the 4 1/2 year period before June 1986 compared with the subsequent period (p < 0.006). Numbers of cases in the low and intermediate score categories declined by about 50% after June 1986, whereas those in the high category fell by 79%. High scorers were more likely to have received aspirin (p < 0.0001) and were older than intermediate and low scorers (p < 0.008). No relation was identified between score and season of onset. CONCLUSIONS: The decline in Reye's syndrome after the aspirin warnings cannot be explained entirely, as has been proposed, by improved diagnosis of 'Reye-like' inherited metabolic and other disorders: this would not account for the greater decline of the high scoring subgroup which also contained those cases most likely to resemble 'classical' Reye's syndrome and to have received aspirin. This study provides further evidence for the role of aspirin in a subset of cases meeting the standard diagnostic criteria for Reye's syndrome and supports the need to consider this disorder as a heterogeneous group of conditions including Reye-like inherited metabolic disorders.     

A novel human homologue of yeast nucleosome assembly protein, 65 kb centromeric to the p57KIP2 gene, is biallelically expressed in fetal and adult tissues

Three genes on 11p15.5 are known to undergo genomic imprinting. The gene for insulin-like growth factor II (IGF2) is normally expressed from the paternal allele, while H19 and p57KIP2, a cyclin-dependent kinase inhibitor, are expressed from the maternal allele. Five germline balanced chromosomal rearrangement breakpoints from patients with Beckwith-Wiedemann syndrome (BWS) have been mapped to 11p15.5 between p57KIP2 and IGF2, and all are derived from the maternal chromosome. By positional cloning from BWS breakpoints, we have isolated a gene 100 kb and 65 kb centromeric to the proximal end of this BWS breakpoint cluster and p57KIP2, respectively. This gene is homologous to yeast nucleosome assembly protein (NAP1) and to a human homologue of NAP1, and we designate it hNAP2 (human nucleosome assembly protein 2). hNAP2 diverges in its expression pattern from IGF2, H19, and p57KIP2, and it shows biallelic expression in all tissues tested. Thus, hNAP2 is functionally insulated from the imprinting domain of 11p15.      

Linkage and physical mapping of X-linked lissencephaly/SBH (XLIS): a gene causing neuronal migration defects in human brain

While disorders of neuronal migration are associated with as much as 25% of recurrent childhood seizures, few of the genes required to establish neuronal position in cerebral cortex are known. Subcortical band heterotopia (SBH) and lissencephaly (LIS), two distinct neuronal migration disorders producing epilepsy and variable cognitive impairment, can be inherited alone or together in a single pedigree. Here we report a new genetic locus, XLIS, mapped by linkage analysis of five families and physical mapping of a balanced X;2 translocation in a girl with LIS. Linkage places the critical region in Xq21-q24, containing the breakpoint that maps to Xq22.3-q23 by high-resolution chromosome analysis. Markers used for somatic cell hybrid and fluorescence in situ hybridization analyses place the XLIS region within a 1 cM interval. These data suggest that SBH and X-linked lissencephaly are caused by mutation of a single gene, XLIS, that the milder SBH phenotype in females results from random X-inactivation (Lyonization), and that cloning of genes from the breakpoint region on X will yield XLIS.      

CD4+ lymphocyte values and trends in individuals infected with Human Immunodeficiency Virus and/or co-infected with Hepatitis C Virus in The Gambia

Objectives

This study was undertaken to monitor the CD4+ lymphocyte count in individuals infected with Human Immunodeficiency Virus (HIV) and/or co-infected with Hepatitis C Virus (HCV) and to compare this with the counts in normal individuals in The Gambia.

Methods

Blood samples were taken from 1500 individuals referred for HIV serology at the Royal Victoria Teaching Hospital (RVTH) following informed consent. Samples were tested for antibodies to HIV by the Murex ELISA, antibodies to HCV by the Ortho ELISA, and CD4 counts determined by the Dynalimmunomagnetic cell isolation method

Results

Of the 1500 patients screened for HIV and HCV antibodies, 6.7% (101/1500) were infected with HIV, 0.6 % (9/1500) were co-infected with HCV and 1.5 % (22/1500) were infected with HCV alone. Almost half (44.6%; 25/56) of HIV-1 infected patients had a CD4+ lymphocyte count at diagnosis of 200 cells/µl or less as compared to 41.7 % (10/24) of HIV-2 and 75% (6/8) of HIV-D infected patients. The rate of CD4 decline was higher among HIV/HCV co-infected persons than individuals infected with HIV or HCV. The rate of decline was higher among men than women. These differences did not reach statistical significance due in large part to the small number of participants who completed the programme. The CD4+ lymphocyte count of apparently healthy Gambian male and females was 489 cells/µl and 496 cells/µl respectively. This rate is lower than that reported for Caucasians, but in agreement with the global range.

Conclusion

A significant progressive decline in CD4+ lymphocyte count was observed among the female control group who were negative for HIV and HCV. This finding is unclear and calls for a longitudinal study involving a cohort of women in this region.Short title: CD4+ counts in HIV/HCV co-infection