Pemphigus Vulgaris Autoantibody Response is Linked to HLA-DQB10503 in Pakistani Patients

ABSTRACT: Pemphigus vulgaris (PV) is an autoimmune disease of the skin and mucous membranes characterized by an autoantibody response against an epidermal cadherin. We performed high resolution HLA class II typing in 19 patients with PV from Rawalpindi, Pakistan and 19 non-Jewish European PV patients from Boston by sequence-specific oligonucleotide probe hybridization. The results were compared with two separate ethnically matched control populations. We found that PV patients from Pakistan had significantly increased frequencies of DRB1*1404 ( p = 0.01), DQA1*0101 ( p = 0.02), and DQB1*0503 ( p = 0.01). Among the patients of non-Jewish European ancestry, DRB1*1401 ( p < 10⁻⁶), DQA1*0101 ( p < 10⁻⁵) and DQB1*0503 ( p < 10⁻⁶), were increased in PV patients. Formal linkage analysis between the major histocompatibility complex and the PV antibody was performed in 67 relatives of the 19 Pakistani patients. The results showed strong evidence for linkage of HLA-DRB1*1404, DQA1*0101, DQB1*0503, with the presence of PV antibody in relatives’ families with a significant logarithm of the odds score of 6.06. Based on the three dimensional structure of class II molecules, we propose that HLA-DQA1*0101 and DQB1*0503, encode a negatively charged P9 peptide binding pocket of the DQ molecule and are significantly associated with susceptibility to PV in non-Jewish populations.     

Dicentric Y chromosome in mixed gonadal dysgenesis.

A 15-year-old girl was investigated because of ambiguous genitalia. Her chromosome studies showed a 45, X/45, Xdic(Yq) mosaicism. The identity of the dicentric Y chromosome was demonstrated by its typical fluorescent banding patterns. Histological evidence of mixed gonadal dysgenesis with intragonadal tumour was observed, confirming the occurrence of gonadoblastoma associated with mosaicism in which at least one cell bears a Y chromosome.     

Use of quantitative competitive PCR to measure Epstein-Barr virus genome load in the peripheral blood of pediatric transplant patients with lymphoproliferative disorders.

A quantitative competitive PCR (QC-PCR) assay for Epstein-Barr virus (EBV) has been developed to provide accurate measurement of EBV genome load in pediatric transplant recipients at risk for developing posttransplant lymphoproliferative disorder (PTLD). The assay quantifies between 8 and 5,000 copies of the EBV genome in 10(5) lymphocytes after a 30-cycle amplification reaction. For 14 pediatric patients diagnosed with PTLD, the median EBV genome load was 4,000, and 13 of the 14 patients had values of >500 copies per 10(5) lymphocytes. Only 3 of 12 control transplant recipients not diagnosed with PTLD had detectable viral genome loads (median value, 40). This median was calculated by using the highest value obtained by PCR testing on each of these patients posttransplantation. PCR values of >500 copies per 10(5) lymphocytes appear to correlate with a diagnosis of PTLD. By a modified protocol, the EBV genome copy number in latently infected adults was estimated to be <0.1 copy per 10(5) lymphocytes.     

Autoantibodies to a regulatory T cell subset in human ageing.

Anti-T cell autoantibodies were detected in some aged humans. Non-immunoglobulin-bearing (Ig-) cells were isolated from the peripheral blood of normal human donors by negative selection through Ficoll, using sheep erythrocytes coated with rabbit anti-human Ig. The Ig- cells were then reacted with sera from 83 individuals ranging in age from 60 to 99 years; 36% of the serum samples were noticeably reactive with the Ig- cells (average reactivity 28%). The peripheral blood lymphocytes from some of the aged individuals were also tested for levels of Ig-secreting cells in a reverse haemolytic plaque assay; there was a six- to eight-fold increase in the number of plaque-forming cells (PFC) from those individuals whose sera contained appreciable amounts of anti-T cell antibody, as compared with those whose sera contained little or no anti-T cell antibody. Isolated Ig- cells from these individuals were also examined for the presence of regulatory T cell subsets, using sera from juvenile rheumatoid arthritis (JRA) patients. The Ig- cells from the subjects who had no detectable anti-T cell antibodies in their sera and near normal PFC levels were reactive with the JRA sera, whereas the Ig- cells from individuals with increased numbers of PFC and with serum anti-T cell antibodies were only slightly reactive with the JRA sera. These data suggest that a majority of the regulatory JRA+ subset of T cells had been lost in the latter group. When sera from aged individuals containing anti-T cell autoantibodies were reacted with JRA-, Ig- cells isolated from a normal human donor, little positive reactivity was seen, indicating that the autoantibodies in sera from aged humans and from some JRA patients are directed against similar T cell subsets.     

Partial trisomy 20 (20q13) and partial trisomy 21 (21pter leads to 21q21.3).

A patient with a double partial trisomy 20 and 21 with mild mental retardation and multiple congenital anomalies is presented. Despite trisomy for a substantial portion of chromosome 21, the patient showed only minor stigmata compatible with Down syndrome.     

The aniridia-Wilms tumor association: The critical role of chromosome band 11p13

The role of del (11)(p13) as a cause of aniridia, with and without Wilms tumor, is strengthened by demonstration of this chromosome aberration in 3 patients: monozygous twin girls, both of whom have aniridia and mental retardation and one of whom has a Wilms tumor; and an unrelated boy with aniridia and ambiguous genitalia. The break points defining the interstitial deletion for the twins are 11p13 and 11p15.1, while for the boy they are 11p1302 and 11p14.1. These patients and their karyotypes substantiate the critical importance of chromosome band 11p13 (or its hemizygous representation) in the development of aniridia and an associated Wilms tumor diathesis, as had been suggested previously (Riccardi VM, Sujansky E, Smith AC, Francke U, (1978): Pediatrics 61, 604-610).     

The role of the thymus in development of lympho-hemopoietic tissues. The effect of thymectomy on development of blood cells,bone-marrow,spleen, and lymph nodes

The effect of thymectomy at different ages in C3H mice on development of circulating leukocytes and cells of marrow, spleen and lymph nodes has been analyzed. Regardless of the age at which thymectomy is performed depression of numbers of circulating lymphocytes is produced. Thymectomy at birth did not affect significantly the relative number of lymphocytes in the marrow during the first few weeks of life, later they fell to low levels. Thymectomy at four weeks was followed by prompt reduction in relative numbers of lymphocytes in the marrow. After reaching six weeks of age, neonatally thymectomized mice showed a high proportion of monocytes in the marrow. Neonatal thymectomy and thymectomy at two weeks of age reduced the number of eosinophils in the marrow. Neonatal thymectomy inhibited development of lymphocytes in the spleen, whereas thymectomy later in life produced only transient depression of lymphocytes in this organ. In addition, neontal thymectomy decreased the relative numbers of small lymphocytes in the lymph nodes. This was associated with drastic depletion of lymphocytes in the deep cortical regions of the nodes.