Mu Heavy Chain Disease

Mu Heavy Chain Disease

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Heavy chain diseases (HCDs) are rare variants of B-cell lymphomas that produce one of three classes of immunoglobulin heavy chains: alpha, gamma, or mu. The clinical manifestations vary with the heavy chain isotype and range from an asymptomatic presentation to aggressive lymphoma. [1]

HCDs characteristically involve production of a mutated immunoglobulin heavy chain that is incapable of either partnering with light chains to form a complete immunoglobulin molecule or incapable of being degraded by a proteasome. Their defining feature is the presence of an abnormal heavy chain in the urine and/or serum without an associated light chain. [2]

Normal immunoglobulin molecules are symmetrical and consist of 2 pairs of polypeptide chains, designated the light and heavy chains, which are interconnected by disulfide bonds. The heavy chains are the larger polypeptide subunits; they are specific and distinctive structures that distinguish the major classes of immunoglobulins.

B cell proliferative disorders that are characterized by an anomalous serum, and sometimes urinary, protein (from free light chain) that is immunochemically related to the Fc fragment of the immunoglobulin molecule are known as HCDs. The isotype of the mutated immunoglobulin heavy chain (α, γ, or µ) determines the nomenclature of HCD subtypes. When the anomalous protein structurally resembles the heavy chain fragment of the immunoglobulin M (IgM) molecule, it is designated as mu-HCD. Ballard and colleagues first described this entity in 1970. [3]

This article focuses on mu-HCD; however, other heavy chain diseases are described (eg, see Heavy Chain Disease, Gamma).

The pathogenesis of mu-HCD is not completely understood. No viruses, chemical, physical, or genetic factors have been identified. [4] Most patients have a concurrent lymphoproliferative disorder resembling chronic lymphocytic leukemia/ small lymphocytic leukemia. There are also single reports of mu-HCD associated with myelodysplastic syndrome, amyloidosis, and diffuse large B cell lymphoma.

In mu-HCD the altered heavy chains contain deletions, insertions, and point mutations that are acquired during somatic hypermutation. These alterations typically result in loss of a large portion of the constant-1 (CH1) domain of the heavy chain, which is responsible for light chain binding. Additionally, this abnormal domain on the heavy chain is also unable to bind to the heat-shock protein 78 (hsp78), which would otherwise promote proteosomal degradation of the aberrant heavy chain. The heavy chain thus bypasses degradation and is instead secreted into the serum, where it can be detected. [2, 5, 6]

United States

Mu-HCD is the least common of the HCDs. Fewer than 50 cases have been reported in the literature. [7] However, many cases likely have not been reported, especially in the past decade. Given the difficulty in diagnosing this disorder, most reports are from the United States, Western Europe, and Scandinavia.

Mu-HCD is predominantly reported in white men in the 5th and 6th decades of life. However, reports also exist in black and Asian patients, with ages ranging from 15-80 years.

The course of mu-HCD is variable. Survival ranges from a few months to several years, with a median survival of 24 months in well-studied cases

Wahner-Roedler DL, Kyle RA. Heavy-Chain Disease. Kaushansky K, Lichtman MA, Prchal JT, Levi MM, Press OW, Burns LJ, Caligiuri MA, eds. Williams Hematology. 9th ed. New York, NY: McGraw-Hill Education; 2016. 1803-14.

Bianchi G, Anderson KC, Harris NL, Sohani AR. The heavy chain diseases: clinical and pathologic features. Oncology (Williston Park). 2014 Jan. 28 (1):45-53. [Medline].

Ballard HS, Hamilton LM, Marcus AJ, Illes CH. A new variant of heavy-chain disease (mu-chain disease). N Engl J Med. 1970 May 7. 282(19):1060-2. [Medline].

Witzig TE, Wahner-Roedler DL. Heavy chain disease. Curr Treat Options Oncol. 2002 Jun. 3(3):247-54. [Medline].

Mihaesco C, Ferrara P, Guillemot JC, et al. A new extra sequence at the amino terminal of a mu heavy chain disease protein (DAG). Mol Immunol. 1990 Aug. 27(8):771-6. [Medline].

Corcos D, Osborn MJ, Matheson LS. B-cell receptors and heavy chain diseases: guilty by association?. Blood. 2011 Jun 30. 117 (26):6991-8. [Medline].

Bianchi G, Anderson KC. Mu heavy chain disease. Atlas of Genetics and Cytogenetics in Oncology and Haematology. Available at http://www.atlasgeneticsoncology.org/Anomalies/MuHeavyChainID1740.html. June 2016; Accessed: October 9, 2017.

Kinoshita K, Yamagata T, Nozaki Y, et al. Mu-heavy chain disease associated with systemic amyloidosis. Hematology. 2004 Apr. 9(2):135-7. [Medline].

Bonhomme J, Seligmann M, Mihaesco C, et al. MU-chain disease in an African patient. Blood. 1974 Apr. 43(4):485-92. [Medline].

Wahner-Roedler DL, Kyle RA. Mu-heavy chain disease: presentation as a benign monoclonal gammopathy. Am J Hematol. 1992 May. 40(1):56-60. [Medline].

Preud’homme JL, Bauwens M, Dumont G, et al. Cast nephropathy in mu heavy chain disease. Clin Nephrol. 1997 Aug. 48(2):118-21. [Medline].

Maisnar V, Tichy M, Stulik J, et al. Capillary immunotyping electrophoresis and high resolution two-dimensional electrophoresis for the detection of mu-heavy chain disease. Clin Chim Acta. 2008 Mar. 389(1-2):171-3. [Medline].

Yanai M, Maeda A, Watanabe N, et al. Successful treatment of mu-heavy chain disease with fludarabine monophosphate: a case report. Int J Hematol. 2004 Feb. 79(2):174-7. [Medline].

Jessica Katz, MD, PhD, FACP Senior Medical Director, Immuno-Oncology, Oncology R&D, GlaxoSmithKline

Jessica Katz, MD, PhD, FACP is a member of the following medical societies: American College of Physicians, American Society of Clinical Oncology, American Society of Hematology

Disclosure: for: Currently employed at GSK.

Kinjal Parikh, MD Resident Physician, Department of Hematology/Oncology, Lankenau Medical Center

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Emmanuel C Besa, MD Professor Emeritus, Department of Medicine, Division of Hematologic Malignancies and Hematopoietic Stem Cell Transplantation, Kimmel Cancer Center, Jefferson Medical College of Thomas Jefferson University

Emmanuel C Besa, MD is a member of the following medical societies: American Association for Cancer Education, American Society of Clinical Oncology, American College of Clinical Pharmacology, American Federation for Medical Research, American Society of Hematology, New York Academy of Sciences

Disclosure: Nothing to disclose.

Sara J Grethlein, MD Associate Dean for Undergraduate Medical Education, Indiana University School of Medicine

Sara J Grethlein, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, American Society of Hematology, American Society of Clinical Oncology

Disclosure: Nothing to disclose.

Paul Schick, MD Emeritus Professor, Department of Internal Medicine, Jefferson Medical College of Thomas Jefferson University; Research Professor, Department of Internal Medicine, Drexel University College of Medicine; Adjunct Professor of Medicine, Lankenau Hospital

Paul Schick, MD is a member of the following medical societies: American College of Physicians, American Society of Hematology

Disclosure: Nothing to disclose.

Ajeet Gajra, MD Associate Professor of Medicine, Director of Hematology/Oncology Fellowship Program, State University of New York Upstate Medical University; Consulting Staff, Department of Internal Medicine, Division of Hematology and Oncology, Veterans Affairs Medical Center

Ajeet Gajra, MD is a member of the following medical societies: American Association for Cancer Research, American Medical Association, American Society of Hematology

Disclosure: Nothing to disclose.

Neerja Vajpayee, MD Associate Professor, Department of Pathology, State University of New York Upstate Medical University

Neerja Vajpayee, MD is a member of the following medical societies: American Society of Hematology, College of American Pathologists, United States and Canadian Academy of Pathology

Disclosure: Nothing to disclose.

Mu Heavy Chain Disease

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