1/119. Heavy chain deposition disease: the disease spectrum. A 45-year-old white woman was found to have microscopic hematuria during her annual physical examination. After a negative urologic workup, she returned 5 months later with nephrotic syndrome, renal insufficiency, and hypocomplementemia. Renal biopsy showed a nodular sclerosing glomerulopathy that could not be further characterized because of inadequate tissue for immunofluorescence. The patient returned 8 months later with chronic renal failure. A repeat renal biopsy showed deposits composed of immunoglobulin g (IgG) heavy chain and complement components C3 and C1 along glomerular, tubular, and vascular basement membranes, with negativity for kappa and lambda light chains, findings consistent with heavy chain deposition disease (HCDD). The heavy chain subclass was exclusively IgG3. Staining with monoclonal antibodies to epitopes of the constant domains of IgG heavy chain showed a CH1 deletion, indicating a truncated heavy chain. On review of the previously reported cases of HCDD, common clinical presentations include nephrotic syndrome, renal insufficiency, hematuria, and, in some cases, hypocomplementemia. In most patients, the hematologic disorder is mild, without overt myeloma. light microscopy shows a nodular sclerosing glomerulopathy, and heavy chain deposits are detectable within basement membranes throughout the kidney by immunofluorescence and electron microscopy. There is no effective treatment for this condition, and virtually all patients progress to chronic renal failure. ( info) |
2/119. Pathological studies on a long-term survived case of gamma heavy chain disease--a brief review of 30 reported cases and a proposal for histological typing. A pathological and brief clinical study on the eleventh case of gamma heavy chain (gamma-chain) disease who died at the age of 44 after a long course of 12 years from the assumed onset of the disease was presented. Clinicopathological observations of the case showed a neoplastic nature which caused her death complicated by asthmatic attacks. autopsy findings were characterized by diffuse infiltration of lymphoplasmacytoid cells and a few large immunoblastic cells into various organs. Literatures of 30 cases reported in the past, and the modern concept of lymphoma strongly suggest that the classificatory position of gamma-chain disease as well as Waldenstrom's macroglobulinemia should be placed between multiple myeloma and classic malignant lymphoma as an independent disease entity belonging to the same category. A proposal of histological typing of the disease was made in order to simplify various diagnostic designations in the literatures:--gamma-chain disease, 1) reticular type, 2) lymphocytic predominance, 3) plasmacytic predominance, 4) lymphoplasmacytoid cell type, 5) immunoblastic type. The present case belongs to type 4. ( info) |
3/119. Gamma heavy chain disease simulating alpha chain disease. A young Turkish girl presented with all the clinicopathological features of a digestive form of alpha chain disease. A gamma heavy chain disease protein, however, was found in her serum and also in the cells invading the intestinal mucosa and mesenteric lymph nodes. ( info) |
4/119. Is there a pathogenic link between gamma heavy chain disease and chronic arthritis? In 1991, gamma heavy chain disease was diagnosed in a 43-year-old female, who 3 years earlier had contracted an erosive seronegative chronic arthropathy. In 1996, her lymphoproliferative disorder required treatment with melphalan and prednisolone. Laboratory studies revealed a gamma3 heavy chain monoclonal component in serum and urine. Massive localization of plasma cells and blasts with cytoplasmic or cell membrane staining for gamma3 chains, but no staining for light chains, was observed by immunohistochemical studies of bone marrow as well as affected synovial tissue. Large amounts of extracellular gamma3-chains were also deposited in the synovial membrane. This is the first documentation of gamma heavy chain deposition disease directly affecting articular structures. Whether it represents the primary pathogenic event followed by reactive inflammatory changes in the joints, or another example of gamma heavy chain disease preceded by chronic arthritis, remains elusive. Regardless, several common cellular and molecular mechanisms discussed here suggest a pathogenic link between the two disease processes. ( info) |
5/119. Nodular glomerulosclerosis secondary to mu heavy chain deposits. mu heavy chain deposition disease is very rare. We report the first case of glomerulonephritis in a woman without evidence of hematopoietic malignancy. Nodular glomerulosclerosis and monotypic mu heavy chain mesangial deposits were identified by immunofluorescence without kappa or lambda deposits. Electron microscopy showed fibrillar mesangial deposits of 16-18 nm in diameter. serum immunoglobulins, cryoglobulins, serum immunoelectrophoresis, and immunofixation, bone marrow biopsy, and Bence Jones proteins in urine were negative. The patient has stable renal disease and is free of malignancy 6 years after the initial occurrence of proteinuria. ( info) |
6/119. Heavy chain deposition disease: recurrence in a renal transplant and report of IgG(2) subtype. Heavy chain deposition disease (HCDD) is a rare entity characterized by tissue deposition of monoclonal heavy chains without light chains. Previous reports of HCDD include gamma(1)-, gamma(3)-, gamma(4)-, and alpha-heavy chain subtypes. Renal transplantation for HCDD has not been previously reported. We report a case of gamma(2)-HCDD in a 67-year-old patient who presented with proteinuria, hematuria, and renal insufficiency and progressed to end-stage renal failure after 6 months. The second case involves a 26-year-old woman who had a renal transplant for HCDD and recurrent gamma(1)-HCDD in the transplant. Neither patient had myeloma. The complete spectrum of gamma-HCDD subtypes has now been reported. Further data are required to make conclusive statements about the true recurrence rate of HCDD in renal transplants. ( info) |
7/119. The amino acid sequence of a monoclonal gamma 3-heavy chain from a patient with articular gamma-heavy chain deposition disease. Abnormal deposition of proteins, including monoclonal immunoglobulin gamma-heavy chains, may cause tissue damage and organ dysfunction. We here report the amino acid sequence of the free gamma-heavy chains present in serum and urine of the first reported case (patient G. L.) of synovial heavy chain deposition disease. The protein was heavily deleted and consisted of the hinge, in addition to the CH2 and CH3 domains, in a dimeric form, thus lacking its variable domain as well as the CH1 domain. The sequence was consistent with the gamma 3 subclass (gamma 3GL). Gm typing revealed the gamma 3 allotypes G3m(b0) and G3m(b1) in accordance with the residues Pro123, Phe128, Thr171 and Phe268 in gamma 3GL. Furthermore, the gamma 3GL molecule was glycosylated at Asn in position 129. Finally, the gamma 3GL protein was shown to contain a typical binding site for the first complement component, C1q, namely the residues Glu150, Lys152 and Lys154, with the potential of binding and activating complement, causing tissue damage following deposition. ( info) |
8/119. mu-chain disease. Report of two new cases. We report two cases of mu-heavy-chain disease. Both patients were affected with a lymphoproliferative disease that shared several suggestive features with the previously reported cases of mu-chain disease: the presence of vacuolated plasma cells in bone marrow, a small amount of alpha 2 moving abnormal mu-chain protein, and urinary kappa bence jones protein in one case. ( info) |
9/119. A case of gamma 3 heavy chain disease with vacuolated plasma cells: a clinical, immunological, and ultrastructural study. A patient with lambda Bence-Jones proteinuria, Waldenstrom's macroglobulinaemia, and Franklin's disease (gamma HCD), but without clinical evidence of a lymphoproliferative disorder, is presented. The serum contained two distinct immunoglobulin abnormalities: a monoclonal immunoglobulin m (IgM) of lambda type, and a protein fragment which was immunologically related to immunoglobulin g (IgG) and devoid of light chain activity. This gamma HCD protein belongs to the gamma 3 subclass with a molecular weight of approximately 60,000 daltons. The urine contained a Bence-Jones lambda protein as well as the gamma HCD fragment. The two paraproteins were probably secreted by two different malignant clones. Ultrastructural study revealed pathological vacuolated plasma cells of a sort that has hitherto been principally described in association with micron HCD. The mechanism of the intracellular storage of pathological immunoglobulins is discussed in the light of the ultrastructural study. ( info) |
10/119. Electrophoretic characterization of a gamma-1-heavy chain disease. This report describes a new case of gamma-1-heavy chain disease found in a woman with malignant lymphoproliferative disease. The patient's serum and urine containing gamma-1-heavy chains were analyzed using different electrophoretic approaches, especially two-dimensional electrophoresis and immunoblotting analysis. In a serum sample, five sets of gamma-1-heavy chain spots differing in molecular weight with acidic pI values and one set of more basic gamma-1-heavy chain spots were found. The major group of spots exhibited molecular weight in the range from 29 to 39 kDa. Examination of urine sample proved the presence of the more basic set of gamma-1-heavy chain spots and two acidic groups, including 29 to 39 kDa set. ( info) |