EurekaMag
+ Translate
+ Most Popular
Gaucher's disease;thirty-two years experience at Siriraj Hospital
A study of Macrobathra Meyrick from China (Lepidoptera, Cosmopterigidae)
First occurrence in ores of tetragonal chalcocite
Effects of trace element nutrition on sleep patterns in adult women
N.Z. range management guidelines. 2. Design of grazing management systems for tussock country
A case of lipoma of the esophagus
A revision of world Acanthosomatidae (Heteroptera: Pentatomidae): keys to and descriptions of subfamilies, tribes and genera, with designation of types
Life history of the coronate scyphozoan Linuche unguiculata (Swartz, 1788)
Perceptual restoration of obliterated sounds
Mutagenicity studies on two chromium(III) coordination compounds
The formation of the skeleton. I. Growth of a long bone. 1st appearance of a center of calcification
Leucopenia and abnormal liver function in travellers on malaria chemoprophylaxis
The joint commission: four key root causes loom large in sentinel event data
Treatment of vitiligo with topical 15% lactic acid solution in combination with ultra violet-A
Behaviour of dairy cows within three hours after feed supply: I. Influence of housing type and time elapsing after feed supply
Observations of the propagation velocity and formation mechanism of burst fractures caused by gunshot
Management and control of patients with type 2 diabetes mellitus in Lebanon: results from the International Diabetes Management Practices Study (IDMPS)
The diet composition and nutritional knowledge of patients with anorexia nervosa
Physoporella croatica Herak, 1958 of the Slovak karst Anisian (Slovakia, the West Carpathians Mts.)
Bright lights, big noise. How effective are vehicle warning systems?
Ein Plesiosaurier-Rest mit Magensteinen aus mittlerem Lias von Quedlinburg
Incidence of Chlamydia trachomatis in patients with sterility
Monster soup: the microscope and Victorian fantasy
Preliminary tests with residual sprays against poultry lice
Duration of the life of plants in phylogeny

Unravelling the immunopathological mechanisms of heavy chain deposition disease with implications for clinical management


Unravelling the immunopathological mechanisms of heavy chain deposition disease with implications for clinical management



Kidney International 91(2): 423-434



ISSN/ISBN: 0085-2538

PMID: 27773425

DOI: 10.1016/j.kint.2016.09.004

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.

Please choose payment method:






(PDF emailed within 0-6 h: $19.90)

Accession: 059203051

Download citation: RISBibTeXText

Related references

Mechanisms of disease: monoclonal immunoglobulin deposition. Amyloidosis, light chain deposition disease, and light and heavy chain deposition disease. Hematology/Oncology Clinics of North America 6(2): 323-346, 1992

Monoclonal immunoglobulin deposition disease: light chain and light and heavy chain deposition diseases and their relation to light chain amyloidosis. Clinical features, immunopathology, and molecular analysis. Annals of Internal Medicine 112(6): 455-464, 1990

Nonamyloidotic monoclonal immunoglobulin deposition disease. Light-chain, heavy-chain, and light- and heavy-chain deposition diseases. Hematology/Oncology Clinics of North America 13(6): 1235-1248, 1999

High-dose melphalan followed by auto-SCT has favorable safety and efficacy in selected patients with light chain deposition disease and light and heavy chain deposition disease. Bone Marrow Transplantation 47(3): 453-455, 2012

Articular, monoclonal gamma3 heavy-chain deposition disease: characterization of a partially deleted heavy-chain gene and its protein product synthesized in vivo and in vitro. Arthritis and Rheumatism 48(11): 3266-3271, 2003

Clinical remission and histopathological resolution of nodular lesions in a patient with gamma3 heavy-chain deposition disease. Clinical Nephrology 69(5): 383-386, 2008

The amino acid sequence of a monoclonal gamma 3-heavy chain from a patient with articular gamma-heavy chain deposition disease. Scandinavian Journal of Immunology 51(6): 602-606, 2000

Monoclonal immunoglobin deposition disease, heavy chain deposition type. American Journal of Kidney Diseases: the Official Journal of the National Kidney Foundation 42(6): A48 E1-2, 2003

A unique case of γ-heavy chain deposition disease characterized by concomitant deposition of γ2 and γ4 subclasses. Internal Medicine 53(22): 2615-2618, 2014

Structure of abnormal heavy chains in human heavy-chain-deposition disease. European Journal of Biochemistry 229(1): 54-60, 1995

Monoclonal gammopathy of renal significance with heavy-chain deposition disease in renal allograft: challenges in the diagnosis and management. Transplant International: Official Journal of the European Society for Organ Transplantation 32(7): 769-770, 2019

Nodal marginal-zone lymphoma associated with monoclonal light-chain and heavy-chain deposition disease. Lancet. Oncology 5(6): 381-383, 2004

Metachronous development of nonamyloidogenic [lambda] light chain deposition disease and IgG heavy chain amyloidosis in the same patient. American Journal of Surgical Pathology 27(11): 1477-1482, 2003

Gamma heavy chain disease: clinical aspects and characterization of a deleted, noncovalently linked gamma1 heavy chain dimer (BAZ). Blood 49(4): 495-505, 1977

A case of monoclonal immunoglobulin light- and heavy-chain deposition disease exhibiting atypical deposition with fibrillary structures, successfully treated with chemotherapy. Clinical Nephrology 64(3): 221-227, 2005