Development of diagnostic antibodies against immunoglobulin heavy chain variable region for heavy chain amyloidosis (AH amyloidosis).
AH amyloidosis
diagnostic antibody
immunoglobulin heavy chain
immunohistochemistry
variable region
Journal
Pathology international
ISSN: 1440-1827
Titre abrégé: Pathol Int
Pays: Australia
ID NLM: 9431380
Informations de publication
Date de publication:
Apr 2021
Apr 2021
Historique:
received:
05
12
2020
accepted:
27
01
2021
pubmed:
14
3
2021
medline:
19
1
2022
entrez:
13
3
2021
Statut:
ppublish
Résumé
It is difficult to diagnose immunoglobulin heavy chain amyloidosis (AH amyloidosis) without proteomic analysis due to no useful diagnostic antibodies. The aim of this study was to develop diagnostic antibodies available to immunohistochemistry and immunoblotting. Two rabbit anti-heavy chain variable region antibodies were generated and evaluated in immunohistochemical studies performed on 11 AH amyloidosis patients and 64 patients with other systemic amyloidoses. Additionally, immunoblotting was performed using extracted amyloid protein from one patient and serum samples from two patients with AH amyloidosis. Immunohistochemical analysis generated a positive outcome in 10 of 11 AH amyloidosis patients (sensitivity 90.9%). While positive staining was also observed in 9 of 64 non-AH amyloidosis patients (specificity 85.9%), substitution of the blocking agent reversed the positive reactivity in 5 of 9 patients. Amyloid protein band was clearly detected via immunoblotting analysis, and protein bands with similar molecular weights of amyloid protein were observed in serum samples from patients with AH amyloidosis. The two antibodies may represent a powerful diagnostic tool for AH amyloidosis. In addition, our data revealed the existence of amyloidogenic variable region fragments in the serum of patients, suggesting their potential as diagnostic markers for AH amyloidosis.
Substances chimiques
Antibodies
0
Immunoglobulin Heavy Chains
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
245-254Subventions
Organisme : Ministry of Education, Culture, Sports, Science and Technology (Japan)
ID : KAKENHI: 17K08739
Organisme : Amyloid Research Committee, Intractable Disease Division, Ministry of Health, Labor and Welfare in Japan
Informations de copyright
© 2021 Japanese Society of Pathology and John Wiley & Sons Australia, Ltd.
Références
Benson MD, Buxbaum JN, Eisenberg DS et al. Amyloid nomenclature 2018: Recommendations by the International Society of Amyloidosis (ISA)nomenclature committee. Amyloid 2018; 25: 215-19.
Kyle RA, Gertz MA. Primary systemic amyloidosis: Clinical and laboratory features in 474 cases. Semin Hematol 1995; 32: 45-59.
Eulitz M, Weiss DT, Solomon A. Immunoglobulin heavy chain-associated amyloidosis. Proc Natl Acad Sci USA 1990; 87: 6542-46.
Solomon A, Weiss DT, Murphy C. Primary amyloidosis associated with a novel heavy-chain fragment (AH amyloidosis). Am J Hematol 1994; 45: 171-76.
Nasr SH, Lobritto SJ, Lauring BP, Arend LJ, D'Agati VD, Markowitz GS. A rare complication of monoclonal gammopathy. Am J Kidney Dis 2002; 40: 867-71.
Mai HL, Sheikh-Hamad D, Herrera GA, Gu X, Truong LD. Immunoglobulin heavy chain can be amyloidogenic: Morphologic characterization including immunoelectron microscopy. Am J Surg Pathol 2003; 27: 541-45.
Copeland JN, Kouides PA, Grieff M, Nadasdy T. Metachronous development of nonamyloidogenic [lambda] light chain deposition disease and IgG heavy chain amyloidosis in the same patient. Am J Surg Pathol 2003; 27: 1477-82.
Yazaki M, Fushimi T, Tokuda T et al. A patient with severe renal amyloidosis associated with an immunoglobulin gamma heavy chain fragment. Am J Kidney Dis 2004; 43: e23-28.
Gono T, Yazaki M, Fushimi T et al. AH amyloidosis associated with lymphoplasmacytic lymphoma secreting a monoclonal gamma heavy chain carrying an unusual truncated D segment. Am J Kidney Dis 2006; 47: 908-14.
Miyazaki D, Yazaki M, Gono T et al. AH amyloidosis associated with an immunoglobulin heavy chain variable region (VH1) fragment: A case report. Amyloid 2008; 15: 125-28.
Sethi S, Theis JD, Leung N et al. Mass spectrometry-based proteomic diagnosis of renal immunoglobulin heavy chain amyloidosis. Clin J Am Soc Nephrol 2010; 5: 2180-87.
Pradhan MA, Henderson RA, Patel D, McGhee CNJ, Vincent AL. Heavy-chain amyloidosis in TGFBI-negative and gelsolin-negative atypical lattice corneal dystrophy. Cornea 2011; 30: 1163-66.
Nasr SH, Said SM, Valeri AM et al. The diagnosis and characteristics of renal heavy-chain and heavy/light-chain amyloidosis and their comparison with renal light-chain amyloidosis. Kidney Int 2013; 83: 463-70.
Manabe S, Hatano M, Yazaki M, Nitta K, Nagata M. Renal AH amyloidosis associated with a truncated immunoglobulin heavy chain undetectable by immunostaining. Am J Kid Dis 2015; 66: 1095-100.
Hassoun Y, Kharfan-Dabaja MA, Baz R. Bortezomib plus dexamethasone results in a late organ response in primary heavy-chain amyloidosis without a hematologic response. Hematol Oncol Stem Cell Ther 2015; 8: 138-39.
Wu HT, Wen YB, Ye W et al. Underlying IgM heavy chain amyloidosis in treatment-refractory IgA nephropathy: A case report. World J Clin Case 2019; 7: 3055-61.
Otaka Y, Goda F, Nakazato Y, Tsutsui T. Systemic heavy- and light chain-amyloidosis presenting nephrotic syndrome and congestive heart failure: A case presentation and literature review. Amyloid 2019; 26: 95-96.
Abe R, Katoh N, Takahashi Y et al. Distribution of amyloidosis subtypes based on tissue biopsy site- consecutive analysis of 729 patients at a single amyloidosis center in Japan. Pathol Int, 71. 70-79. https://doi.org/10.1111/pin.13041
Ichimata S, Kobayashi M, Shimojo H, Katoh N, Yazaki M, Kanno H. Usefulness of gastroduodenal biopsy in the differential diagnosis of systemic AH amyloidosis from systemic AL amyloidosis. Histopathology 2018; 73: 230-39.
Kim WS, Nishizawa T, Yoshimizu M. Non-specific adsorption of fish immunoglobulin M (IgM) to blocking reagents on ELISA plate wells. Dis Aquat Organ 2007; 78: 55-59.
Bergström J, Murphy CL, Weiss DT et al. Two different types of amyloid deposits-apolipoprotein A-IV and transthyretin-in a patient with systemic amyloidosis. Lab Invest 2004; 84: 981-88.
Mahmood S, Gilbertson JA, Rendell N et al. Two types of amyloid in a single heart. Blood 2014; 124: 3025-27.
Tan SY, Murdoch IE, Sullivan TJ et al. Primary localized orbital amyloidosis composed of the immunoglobulin gamma heavy chain CH3 domain. Clin Sci 1994; 87: 487-91.
Solomon A, Frangione B, Franklin EC. Bence Jones proteins and light chains of immunoglobulins. Preferential association of the V lambda VI subgroup of human light chains with amyloidosis AL (lambda). J Clin Invest 1982; 70: 453-56.