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S Jablonska

Publications and source records attributed to S Jablonska.

At least 19 recordsLinked to original sources
PubMed2003

Genetic and functional analyses of FH mutations in multiple cutaneous and uterine leiomyomatosis, hereditary leiomyomatosis and renal cancer, and fumarate hydratase deficiency.

Germline mutations of the fumarate hydratase (FH, fumarase) gene are found in the recessive FH deficiency syndrome and in dominantly inherited susceptibility to multiple cutaneous and uterine leiomyomatosis (MCUL). We have previously reported a number of germline FH mutations from MCUL patients. In this study, we report additional FH mutations in MCUL and FH deficiency patients. Mutations can readily be found in about 75% of MCUL cases and most cases of FH deficiency. Some of the more common FH mutations are probably derived from founding individuals. Protein-truncating FH mutations are functionally null alleles. Disease-associated missense FH changes map to highly conserved residues, mostly in or around the enzyme's active site or activation site; we predict that these mutations severely compromise enzyme function. The mutation spectra in FH deficiency and MCUL are similar, although in the latter mutations tend to occur earlier in the gene and, perhaps, are more likely to result in a truncated or absent protein. We have found that not all mutation-carrier parents of FH deficiency children have a strong predisposition to leiomyomata. We have confirmed that renal carcinoma is sometimes part of MCUL, as part of the variant hereditary leiomyomatosis and renal cancer (HLRCC) syndrome, and have shown that these cancers may have either type II papillary or collecting duct morphology. We have found no association between the type or site of FH mutation and any aspect of the MCUL phenotype. Biochemical assay for reduced FH functional activity in the germline of MCUL patients can indicate carriers of FH mutations with high sensitivity and specificity, and can detect reduced FH activity in some patients without detectable FH mutations. We conclude that MCUL is probably a genetically homogeneous tumour predisposition syndrome, primarily resulting from absent or severely reduced fumarase activity, with currently unknown functional consequences for the smooth muscle or kidney cell.

Amino Acid Metabolism, Inborn Errors↗
PubMed2003

Pemphigus herpetiformis with IgA and IgG antibodies to desmoglein 1 and IgG antibodies to desmocollin 3.

We describe a case with clinical and histologic features of pemphigus herpetiformis associated with IgG and IgA anti-keratinocyte cell surface antibodies to desmoglein 1 (Dsg1) and exclusively IgG antibodies to desmocollin 3 (Dsc3). The clinical presentation was somewhat similar to IgA pemphigus; the main difference was the prevailing association with IgG antibodies to Dsg1. The presence of IgA anti-Dsg1 antibodies was confirmed by IgA enzyme-linked immunosorbent assay and IgG anti-Dsc3 antibodies were detected by a novel enzyme-linked immunosorbent assay with the use of baculovirus expressing recombinant Dscs for IgG and IgA. The reactivity of IgG antibodies with Dsc3 was confirmed by COS-7 cell cDNA transfection method using cDNA of human Dsc1 to Dsc3. We discuss the differentiation of pemphigus herpetiformis, associated with both IgG and IgA antibodies, from IgA pemphigus, particularly in regard to the autoimmune reaction with Dsgs and Dscs.

Adult↗
PubMed2002

Celiac disease and immunoglobulin a deficiency: how effective are the serological methods of diagnosis?

Immunoglobulin A (IgA) deficiency is 10 to 15 times more common in patients with celiac disease (CD) than in healthy subjects. Serological tests have become the preferred methods of diagnosing CD in both symptomatic and asymptomatic patients. However, commercially available serological methods are limited in that they detect only the IgA isotype of antibodies (with the exception of IgG gliadin assays); hence, IgA-deficient patients with CD may yield false-negative serology. Fifteen pediatric patients with CD and 10 IgA-deficient pediatric patients without CD were examined for IgA and IgG antibodies to endomysium, gliadin, and tissue transglutaminase. Twenty-five specimens from patients with IgA deficiency were examined. Fifteen were from patients with CD, and 10 were patients without CD. All 15 IgA-deficient patients with CD were positive for endomysium antibodies of the IgG isotype and for IgG gliadin antibodies. All but one of the IgA-deficient patients with CD were also positive for IgG tissue transglutaminase antibodies. None of the IgA-deficient patients without CD were positive for any of the antibody markers. All the specimens examined were also negative for IgA-specific antibodies to endomysium, gliadin, and tissue transglutaminase. IgG-specific antibody tests for endomysium, gliadin, and tissue transglutaminase are useful for the identification of IgA-deficient patients with CD. IgG antibody tests along with tests routinely being used in clinical laboratories can reliably detect all active patients with CD. In addition, the levels of these CD-specific IgG antibodies could be used to monitor patient dietary compliance.

Adolescent↗
PubMed2002

Intravenous immunoglobulins control scleromyxoedema.

BACKGROUND: Scleromyxoedema is a variant of papular mucinosis affecting the skin and internal organs. The different therapeutic approaches proposed for scleromyxoedema are still unsatisfactory. Intravenous immunoglobulin (IVIg) has been successfully employed in the treatment of connective tissue diseases and vasculitides. PATIENTS: The successful treatment of three cases of scleromyxoedema with IVIg is reported here. CONCLUSIONS: The relatively low risk of the drug and the high effectiveness seen in three patients suggest that IVIg is a new treatment potentially useful in scleromyxoedema.

Adult↗
PubMed2001

Tissue transglutaminase and endomysial antibodies-diagnostic markers of gluten-sensitive enteropathy in dermatitis herpetiformis.

The association of Durhing's disease, commonly referred to as dermatitis herpetiformis (DH), with gluten-sensitive enteropathy (GSE) is supported by the presence of villous atrophy and endomysial antibodies (EMA). EMA are found to be a marker of GSE both in celiac disease (CD) and in DH. Since tissue transglutaminase (tTG) is believed to be the major autoantigen in GSE, the aim of our study was to determine the specificity and sensitivity of anti-tTG antibody ELISA compared to the EMA indirect immunofluorescence test. We studied 44 cases of DH, confirmed by the presence of IgA immune deposits in the dermal papillae, and 58 cases of CD conforming to the International Criteria of Diagnosing CD. The control group comprised 161 sera from patients with vesiculobullous disorders other than DH and 106 sera from normal healthy blood donors. Anti-tTG antibodies were detected in 36 of 44 DH (79%) and in 32 of 58 CD (55%) patients. EMA were positive in 33 of 44 DH (74%) and in 36 of 58 CD (62%) patients. Both the EMA and the antibodies to tTG were present in the majority of patients with DH and CD when they were on a normal gluten-containing diet and were absent when on a gluten-free diet for an extended period of time. There were, however, small discrepancies in positivity and negativity in tTG antibody-positive and EMA-negative patients and vice versa. There seems to be a correlation between the EMA titers and the anti-tTG antibody levels. This study confirms the high specificity and sensitivity of anti-tTG antibody ELISA for GSE and its strong correlation with EMA both in CD and in DH. The results of anti-tTG antibody and EMA assays were comparable; however, in DH, tTG was somewhat more sensitive than the EMA test. For screening of DH, it is advisable to perform both EMA and anti-tTG antibody tests.

Autoantibodies↗
PubMed2001

Mutation and abnormal expression of the p53 gene in the viral skin carcinogenesis of epidermodysplasia verruciformis.

Patients suffering from epidermodysplasia verruciformis are prone to nonmelanoma skin cancers, due to an inherited abnormal susceptibility to the oncogenic human papillomavirus type 5. Genotoxic sunlight ultraviolet B radiations are likely to be a cofactor. Lesions of two human-papillomavirus-type-5-infected epidermodysplasia verruciformis patients collected during an 8 y period were retrospectively studied for p53 mutations in exons 5 through 8 by a polymerase chain reaction single-strand conformation polymorphism technique and/or by DNA sequencing of amplified exons. Mutations were detected in 11 of 26 (42.3%) specimens, including five (62.5%) squamous cell carcinomas, three (33.3%) Bowen's carcinomas in situ, two (40%) actinic keratoses, and one (33%) benign lesion. The nine mutations characterized by sequencing were shown to be missense and to affect mutational hotspots in human cancers. Five were C-->T transitions at dicytidine sites considered as ultraviolet signature mutations. Two were transversions (C-->G and C-->A) at dicytidine sites and two were C-->T transitions at nondipyrimidine sites. A marked p53 immunoreactivity was disclosed in 72.7% of 11 invasive carcinomas, 55.6% of nine carcinomas in situ, 37.5% of eight actinic keratoses, and one of three benign lesions. This includes 81.8% of 11 specimens with a p53 mutation but also 50% of 14 specimens with no mutation detected. A dysfunction of the p53 gene is thus likely to play a part in epidermodysplasia verruciformis carcinogenesis, either due to ultraviolet-B-induced p53 mutations, as in nonmelanoma skin cancers in the general population, or involving other mutagens or mechanisms. The part played by human papillomavirus type 5 proteins expressed in epidermodysplasia verruciformis keratinocytes remains to be determined.

Adult↗