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Biomedical subjects

J J Zone

Publications and source records attributed to J J Zone.

At least 19 recordsLinked to original sources
PubMed2001

A strategy for high throughput HLA-DQ typing.

We have developed a high throughput HLA typing methodology that is a modification of the standard sequence-specific primer method. This approach is distinct from other methods using an automated DNA analyzer, as more than one gene is typed in a single lane. We have optimized the method for use on an ABI 373 automated genotyping machine. Primers were designed to preferentially amplify DNA fragments of the generic allelic groups of the DQA1 and DQB1 loci. PCR products representing alleles at the DQA1 locus were amplified using a different fluorescent dye than the PCR products from the DQB1 locus. Only three PCR reactions are required for low resolution typing of DQA1 and DQB1. Use of different labeled primers enables genotyping for both loci in a single gel lane, allowing for 64 samples to be typed at low resolution for both DQA1 and DQB1 on a single gel. Automated allele assignments were determined based on DNA migration distance through a polyacrylamide gel using a standard genotype allele-calling program. Accuracy of this method is greater than 98% for both loci. The strategy described here may be adapted to include more loci or to produce higher resolution typing of alleles encoded by these loci. It can be readily optimized for use on other slab gel or capillary electrophoresis systems.

Alleles↗
PubMed2001

Linkage analysis of HLA and candidate genes for celiac disease in a North American family-based study.

BACKGROUND: Celiac disease has a strong genetic association with HLA. However, this association only explains approximately half of the sibling risk for celiac disease. Therefore, other genes must be involved in susceptibility to celiac disease. We tested for linkage to genes or loci that could play a role in pathogenesis of celiac disease. METHODS: DNA samples, from members of 62 families with a minimum of two cases of celiac disease, were genotyped at HLA and at 13 candidate gene regions, including CD4, CTLA4, four T-cell receptor regions, and 7 insulin-dependent diabetes regions. Two-point and multipoint heterogeneity LOD (HLOD) scores were examined. RESULTS: The highest two-point and multipoint HLOD scores were obtained in the HLA region, with a two-point HLOD of 3.1 and a multipoint HLOD of 5.0. For the candidate genes, we found no evidence for linkage. CONCLUSIONS: Our significant evidence of linkage to HLA replicates the known linkage and association of HLA with CD. In our families, likely candidate genes did not explain the susceptibility to celiac disease.

Journal Article↗
PubMed2001

Prevalence and clinical characteristics of celiac disease in Downs syndrome in a US study.

Celiac disease is an autoimmune gastrointestinal disorder characterized by mucosal atrophy of the jejunum on exposure to gluten, a protein found in grains. The purpose of our study was to determine the prevalence of celiac disease in children with Downs syndrome in a U.S.-based Caucasian population. The 97 Downs syndrome children were screened for celiac disease using serum IgA-anti-endomysial antibody testing, which is highly specific and sensitive for the disorder. Children with titers greater than 1:5 (using the IgA endomysial antibody [EMA] test; EMA+) were considered affected. Ten children (10.3%) were EMA+. We examined their HLA DQA1 DQB1 genotype, karyotype, clinical characteristics, and the prevalence of celiac disease in their first-degree relatives. The nine available karyotypes were trisomy 21. Downs syndrome-specific mean height percentile was 64%+/-26% (range <5-99%) and weight percentile was 43%+/-28% (range 5-95%). Presence of diarrhea, constipation, vomiting, and abdominal pain was similar for children with and without celiac disease. Only bloating symptoms were significantly more frequent in those with celiac disease (EMA+). Seven of eight (88%) genotyped EMA+ children had the celiac disease-associated high-risk HLA DQA1*0501 DQB1*0201 genotype as compared with 13/ 80 (16%) of EMA- children. Five of 48 (10%) first-degree relatives of the celiac disease (EMA+) children were EMA+. In conclusion, celiac disease, as diagnosed by positive endomysial antibody tests, has an increased prevalence in children with Downs syndrome in the U.S. as compared with the general population (1/250). Clinical and growth characteristics do not distinguish between children with and without celiac disease. Based on these observations, it is recommended that children with Downs syndrome be screened for celiac disease.

Adolescent↗
PubMed2001

Basal cell carcinomas are populated by melanocytes and Langerhans [correction of Langerhan's] cells.

Several reports have documented the coexistence of basal cell carcinoma (BCC) with other lesions, including melanoma. This study was performed to determine whether nests of BCC contain benign melanocytes and Langerhans [corrected] cells. Ten cases of BCC were investigated to determine whether benign melanocytes and Langerhans [corrected] cells populate tumor nests. The BCCs were stained with antibodies to cytokeratin AEI/AE3, S-100, HMB-45, Melan-A, and CD1a proteins. We report that all 10 BCCs were populated by dendritic melanocytes distributed at the periphery (5/10 cases) or evenly throughout tumor nests (5/10 cases). Clusters of melanocytes were not identified in any of the BCCs. A total of 9 of 10 tumors showed staining of dendritic Langerhans cells with CD1a. A total of 8 of 10 tumors stained with cytokeratin AEI/AE3; in 6 of the 8 tumors, the staining was focal. We compared these findings with a single example of a BCC and melanoma in situ (MIS) collision tumor in which the cytokeratin AE1/AE3-positive epithelial nests of BCC were populated by a high density of malignant melanocytes that stained with S-100 and HMB-45. Melanocytes were disposed singly and in clusters of two or more cells within BCC tumor nests. We conclude from this study that BCCs are regularly populated by benign melanocytes and Langerhans [corrected] cells. Furthermore, when BCC is infiltrated with malignant melanocytes of MIS, the melanocyte density is higher and clusters of melanocytes can be observed. The significance of these two findings is unclear, as additional cases of BCC MIS collision tumor need to be studied.

Antigens, Neoplasm↗
PubMed2001

Linear IgA bullous dermatosis responsive to a gluten-free diet.

Dermatitis herpetiformis is associated with a gluten-sensitive enteropathy in >85% of cases. Both the skin lesions and the enteropathy respond to gluten restriction. Linear IgA bullous dermatosis has a much lower prevalence of histological small bowel abnormalities, and lesions are not known to respond to gluten restriction. We report a patient with linear IgA bullous dermatosis and gluten-sensitive enteropathy. This report addresses the issue of whether linear IgA bullous dermatosis can be associated with gluten-sensitive enteropathy. We evaluated the response to gluten restriction and normal diet by following the status of the patient's jejunal biopsies and skin lesions. The patient responded to gluten restriction, as shown by resolution of jejunal abnormalities and skin lesions and subsequently by recurrence of jejunal abnormalities and skin lesions with reinstitution of a gluten-containing diet. This report demonstrates that linear IgA bullous dermatosis can respond to gluten restriction if an underlying gluten-sensitive enteropathy is present.

Adult↗
PubMed2000

Relapsing Henoch-Schönlein purpura associated with Pseudomonas aeruginosa pyelonephritis.

Henoch-Schönlein purpura is a systemic vasculitis of unknown cause. It is frequently triggered by a streptococcal upper respiratory tract infection. Other bacteria have been implicated as triggering agents. We report a recurring case of Henoch-Schönlein purpura in a patient with Pseudomonas pyelonephritis. The Henoch-Schönlein purpura remitted only when the infection was eradicated. Pseudomonas infection should be added to the list of bacteria that can trigger Henoch-Schönlein purpura.

Adult↗
PubMed2000

Plasmapheresis as a steroid saving procedure in bullous pemphigoid.

BACKGROUND: Bullous pemphigoid is an immunobullous disease affecting predominantly older patients. In severe cases, high-dose corticosteroids and/or other immunosuppressants are often needed long term to control the disease. These can be associated with serious side-effects in this patient population. Objective To evaluate the benefit of plasmapheresis as a steroid saving agent in a cohort of 10 patients. RESULTS: Plasmapheresis was effective as a steroid saving therapy. All patients went into remission with a lower daily dosage of oral prednisone at 3 and 6 months postplasmapheresis. Two patients had side-effects from therapy that, while significant, did not interfere with long-term improvement in their disease. Eight patients had circulating immunoglobulin G (IgG) antibodies reactive with bullous pemphigoid antigen 1, and three of these had circulating antibodies reactive with bullous pemphigoid antigen 2 on Western immunoblot. CONCLUSIONS: Plasmapheresis was an effective steroid sparing therapy in these patients. Due to its high cost and potential morbidity, plasmapheresis should not be recommended as routine therapy for bullous pemphigoid, but it is a useful adjunct in resistant cases.

Adult↗
PubMed1999

Plasmapheresis as an adjunct treatment in toxic epidermal necrolysis.

BACKGROUND: Toxic epidermal necrolysis (TEN) is a severe, progressive disease characterized by the sudden onset of skin necrosis. It is frequently associated with systemic involvement and has a high rate of morbidity and mortality. Standard therapy includes meticulous wound care, fluid replacement, and nutritional support in an intensive care setting. OBJECTIVE: We evaluated the outcomes of patients treated in a burn unit for TEN over a 9-year period and compared the outcomes of a subset of patients treated with plasmapheresis with those managed by conventional means. METHODS: The records of 16 patients with a diagnosis of TEN obtained from a computerized database were reviewed. Parameters recorded included extent of body surface area involvement and number of mucous membranes involved at admission, complications such as sepsis or need for mechanical ventilation, length of stay, and disposition. RESULTS: Sixteen patients were included in this study. Ten were treated with conventional support measures alone. Six were treated with plasmapheresis. The average age was 42.4 years; the male/female ratio was 1:2.2. Sulfamethoxazole/trimethoprim was implicated in causation in 6 patients. The average extent of involvement on admission in all patients was 51.5% total body surface area. The average length of stay in all patients was 14.8 days. Eight patients (50%) were discharged home, 4 (25%) were discharged to a rehabilitation facility, and 4 (25%) died (2 of sepsis, 2 of cardiopulmonary arrest). None of the plasmapheresis-treated patients died. CONCLUSION: Plasmapheresis is a safe intervention in extremely ill TEN patients and may reduce the mortality in this severe disease. Prospective studies are needed to further define its usefulness.

Adolescent↗
PubMed1999

Characterization of the antibody response in oesophageal cicatricial pemphigoid.

Cicatricial pemphigoid (CP) is a subepidermal, autoimmune bullous dermatosis. It is classified as a clinical subset of bullous pemphigoid (BP). However, it differs from BP in some significant ways: (i) in CP mucosal involvement with clinical scarring is prominent; (ii) there is a prominent IgA class antibody response alone or in addition to the IgG class antibody response; and (iii) there is a heterogeneous antibody response in CP, whereas in BP the majority of the antibodies are directed against a 180-kDa hemidesmosomal protein, bullous pemphigoid antigen 2 (BPAg2). Oesophageal involvement in CP is a rare, but often devastating manifestation. In this study we examined the humoral autoimmune response in oesophageal CP, in an attempt to characterize the autoantibody reactivity profile. We used direct and indirect immunofluorescence and Western immunoblotting using normal human skin and oesophagus substrates. We studied patient sera over time in order to search for evidence of epitope spreading in these patients. All patients had positive direct immunofluorescence of perilesional oesophageal epithelium. All patients had positive circulating antibasement membrane zone autoantibody titres. There was a significant IgA class in addition to an IgG class autoantibody response. IgA and IgG antibodies demonstrated significant reactivity with BPAg2 and the 97 kDa linear IgA disease antigen on Western immunoblot suggesting intraprotein epitope spreading. There was no evidence of interprotein epitope spreading over time. Our findings suggest that there is a heterogeneous antibody response in oesophageal CP with the predominant antigen being BPAg2.

Autoantibodies↗
PubMed1999

IgA1 is the major IgA subclass in cutaneous blood vessels in Henoch-Schönlein purpura.

Henoch-Schönlein purpura (HSP) is characterized by palpable purpura predominantly involving the lower extremities. On direct immunofluorescence IgA can be seen deposited in the blood vessel walls of the superficial dermis. The subclass distribution of antibodies to this IgA was studied in the biopsies of 28 patients with HSP by direct immunofluorescence using anti-IgA1 and anti-IgA2 specific monoclonal antibodies. All 28 patients' biopsies demonstrated deposition of IgA1 while only one patient had IgA2 deposition. Positive and negative controls stained appropriately. This demonstrates that IgA1 is the dominant IgA subclass found in the skin in Henoch-Schönlein purpura.

Capillaries↗
PubMed1999

Bullous pemphigoid sera that contain antibodies to BPAg2 also contain antibodies to LABD97 that recognize epitopes distal to the NC16A domain.

IgG antibodies from the sera of some patients with bullous pemphigoid (BP) react with a 180 kDa protein termed BPAg2. Antibodies in BP are directed to an extracellular noncollagenous domain of this protein termed NC16A. Our group has recently shown that a portion of the extracellular domain of BPAg2 is identical to LABD97 on the basis of amino acid sequencing. We evaluated sera from 33 patients with BP with circulating IgG antibodies on indirect immunofluorescence, which stained the epidermal side of split skin with titers ranging from 1:40 to 1:640. Immunoblotting was performed against (i) two preparations of proteins from epidermal extract, one containing BPAg2 and one containing LABD97, and (ii) the recombinant NC16A domain of the BPAg2 protein. Twelve sera reacted with the BPAg2 protein. Ten of these also reacted strongly with the NC16A domain. Nine of the 12 sera also reacted with the LABD97 antigen. Bound antibodies were eluted from the 97 kDa band and reapplied to split skin where they bound to the epidermal side. The eluted antibodies also reacted to the BPAg2 protein from the epidermal extract, but did not react with the NC16A domain on immunoblot. We conclude that these nine sera react with an epitope present within BPAg2 and LABD97 but not within the NC16A domain. This epitope is therefore distal to the previously described epitopes in BP. In BP, epitope spreading may occur and antibodies may be produced that recognize the distal portion of the BPAg2 molecule identical to LABD97 but that do not involve the NC16A domain.

Antibodies↗
PubMed1999

IgA antibodies recognizing LABD97 are predominantly IgA1 subclass.

Linear IgA bullous dermatosis is a rare acquired subepidermal blistering disease of the skin. A recognized antigen in linear IgA bullous dermatosis is a 97-kDa basement membrane zone protein termed LABD97. Previous studies, using immunofluorescent techniques, have suggested that the IgA response is restricted to the IgA1 subclass. We studied the IgA antibody subclasses in the sera of 6 patients that contained circulating IgA antibodies reactive with LABD97. The methods used included direct and indirect immunofluorescence and Western immunoblot. All patients tested had IgA1 anti-LABD97 antibodies detected by all 3 methods. Two patients had IgA2 antibodies detected by direct immunofluorescence. Three patients had IgA2 antibodies on indirect immunofluorescence. Two of these also had anti-LABD97 IgA2 antibodies and 1 had secretory component containing anti-LABD IgA antibodies on Western immunoblot. We conclude that the predominant IgA antibody subclass reactive with LABD97 in LABD is IgA1, although the IgA2 subclass may be involved in some cases.

Adult↗
PubMed1999

Localized bullous pemphigoid in a patient with B-cell lymphoma.

Bullous pemphigoid (BP) is an immunobullous disease characterized by circulating IgG antibodies directed towards cutaneous basement zone antigens. We report the case of a patient who had BP localized to a stoma site. At initial examination, a nodule was noted on the temple, which proved to be a large cell lymphoma, B-cell phenotype. On Western immunoblot, the patient's serum showed circulating IgG antibodies reactive with the 230 kDa BP antigen and the 97 kDa linear IgA bullous dermatosis antigen. The co-incident onset of the two diseases suggest that this may represent a case of paraneoplastic BP.

Aged↗
PubMed1999

The immunoglobulin A antibody response in clinical subsets of mucous membrane pemphigoid.

BACKGROUND: Mucous membrane pemphigoid (MMP) is an immunobullous disease. In MMP there is frequently a mixed antibody response with the presence of IgA and/or IgG antibodies directed toward basement membrane zone antigens. The IgG antibody response in MMP has been studied, but the antigens to which the IgA antibodies react have not been studied. OBJECTIVE: To determine the IgA autoantibody reactivity profiles in patients with MMP. METHODS: Patients who had both ocular and oral MMP were compared with patients who had ocular or oral MMP and with patients who had cutaneous linear IgA disease (LABD) by Western immunoblot studies. RESULTS: Five of 15 MMP patients and 1 of 5 LABD patients had IgA antibodies reactive with the 180-kD bullous pemphigoid antigen. Seven of 15 MMP patients had IgA antibodies reactive with the 97-kD LABD antigen. CONCLUSION: Major antigens in IgA MMP are the 180-kD bullous pemphigoid antigen and the 97-kD LABD antigen.

Autoantibodies↗