• MeSH
• akridiny farmakologie   MeSH
• alergeny imunologie   MeSH
• alergie imunologie   MeSH
• B-lymfocyty účinky léků   imunologie   MeSH
• G-kvadruplexy * MeSH
• kultivované buňky MeSH
• myši inbrední BALB C MeSH
• ovalbumin imunologie   MeSH
• přesmyk imunoglobulinových tříd * MeSH
• zánět imunologie   MeSH
• zvířata MeSH
• Check Tag
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• dopisy MeSH
• práce podpořená grantem MeSH

Randall-type heavy chain deposition disease (HCDD) is a rare disorder characterized by tissue deposition of a truncated monoclonal immunoglobulin heavy chain lacking the first constant domain. Pathophysiological mechanisms are unclear and management remains to be defined. Here we retrospectively studied 15 patients with biopsy-proven HCDD of whom 14 presented with stage 3 or higher chronic kidney disease, with nephrotic syndrome in 9. Renal lesions were characterized by nodular glomerulosclerosis, with linear peritubular and glomerular deposits of γ-heavy chain in 12 patients or α-heavy chain in 3 patients, without concurrent light chain staining. Only 2 patients had symptomatic myeloma. By serum protein electrophoresis/immunofixation, 13 patients had detectable monoclonal gammopathy. However, none of these techniques allowed detection of the nephrotoxic truncated heavy chain, which was achieved by immunoblot and/or bone marrow heavy chain sequencing in 14 of 15 patients. Serum-free kappa to lambda light chain ratio was abnormal in 11 of 11 patients so examined. Immunofluorescence studies of bone marrow plasma cells showed coexpression of the pathogenic heavy chain with light chain matching the abnormal serum-free light chain in all 3 tested patients. Heavy chain sequencing showed first constant domain deletion in 11 of 11 patients, with high isoelectric point values of the variable domain in 10 of 11 patients. All patients received chemotherapy, including bortezomib in 10 cases. Renal parameters improved in 11 patients who achieved a hematological response, as assessed by normalization of the free light chain ratio in 8 cases. Tissue deposition in HCDD relates to physicochemical peculiarities of both variable and constant heavy chain domains. Early diagnosis and treatment with bortezomib-based combinations appear important to preserve renal prognosis. Thus, monitoring of serum-free light chain is an indirect but useful method to evaluate the hematological response.

• MeSH
• biopsie MeSH
• bortezomib terapeutické užití   MeSH
• chronická renální insuficience farmakoterapie   imunologie   patologie   MeSH
• fluorescenční protilátková technika MeSH
• glomerulonefritida farmakoterapie   imunologie   patologie   MeSH
• imunoglobuliny - alfa-řetězce analýza   MeSH
• imunoglobuliny - gama-řetězce analýza   genetika   MeSH
• imunoglobuliny - kappa-řetězce analýza   MeSH
• imunoglobuliny - lambda-řetězce analýza   MeSH
• kombinovaná farmakoterapie MeSH
• ledviny účinky léků   imunologie   patologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• nefrotický syndrom farmakoterapie   imunologie   patologie   MeSH
• nemoc z těžkých řetězců farmakoterapie   genetika   imunologie   patologie   MeSH
• nemoci ledvin farmakoterapie   imunologie   patologie   MeSH
• paraproteinemie farmakoterapie   imunologie   MeSH
• polymerázová řetězová reakce MeSH
• retrospektivní studie MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• výsledek terapie MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Francie MeSH

Gliadins, and primarily α-gliadins containing several sequences such as aa 31-49, aa 56-88 (33-mer), aa 57-68, and aa 69-82, are critical in the induction of immune response or toxic reaction leading to the development of celiac disease (CLD). The role of IgA anti-gliadin antibodies (IgA AGA) is unknown. To this end, we prepared several humanized monoclonal IgA AGA using transgenic α1KI mice. Employing Pepscan with overlapping decapeptides of α-gliadin we observed a robust similarity between the specificity of humanized mouse monoclonal IgA AGA and IgA AGA from patients with florid CLD. The common immunodominant region included several sequential epitopes localized in the N-terminal part of α-gliadin (QFQGQQQPFPPQQPYPQPQPFP, aa 29-50, and QPFPSQQPYLQL, aa 47-58). Notably, IgA AGA produced by clones 8D12, 15B9, 9D12, and 18E2 had significant reactivity against sequences localized in the 33-mer, LQLQPFPQPQ (aa 56-65) and PQLPYPQPQPFL (aa 69-80). Humanized mouse monoclonal IgA AGA that have a known specificity are suitable as standard in ELISAs to detect serum IgA AGA of CLD patients and for studying the AGA pathogenic role in CLD, especially for analyzing the translocation of complex of specific IgA antibodies and individual gliadin peptides through enterocyte barrier.

• MeSH
• celiakie imunologie   MeSH
• dospělí MeSH
• epitopy chemie   imunologie   MeSH
• gliadin imunologie   MeSH
• imunoglobulin A imunologie   MeSH
• lidé MeSH
• mladiství MeSH
• molekulární sekvence - údaje MeSH
• monoklonální protilátky biosyntéza   imunologie   MeSH
• myši transgenní imunologie   MeSH
• myši MeSH
• sekvence aminokyselin MeSH
• specificita protilátek MeSH
• zvířata MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH