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.

• Klíčová slova
• free light chains, glomerulosclerosis, immunoglobulin heavy chains, monoclonal gammopathy,
• 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
• Názvy látek
• bortezomib MeSH
• CHA heavy chain disease protein, human MeSH Prohlížeč
• heavy chain disease proteins, human MeSH Prohlížeč
• imunoglobuliny - alfa-řetězce MeSH
• imunoglobuliny - gama-řetězce MeSH
• imunoglobuliny - kappa-řetězce MeSH
• imunoglobuliny - lambda-řetězce MeSH