Gamma Heavy Chain Disease with T-cell Large Granular Lymphocytic Leukemia: A Case Report and Review of the Literature

Systemic lupus erythematosus (SLE) is characterized by the overproduction of highaffinity autoreactive antibodies. Here, we show that more than 65.8% of 222 recombinant antibodies derived from 8 SLE patients can be secreted as heavy chain-only antibodies (HCAbs) when expressed in HEK-293T cells. The secretion of HCAbs follows the conventional endoplasmic reticulum-Golgi apparatus pathway, despite triggering a weaker unfolded protein response (UPR). Many of the purified SLE HCAbs remain autoreactive and have an even higher affinity for dsDNA, Sm, nucleosome, and cardiolipin than HCAbs from healthy individuals. Extended analyses of the CDR3 region and the heavy chain variable (VH) region of HCAb F3 show that the VH region is responsible for IgH secretion, while the CDR3 region determines its reactivity. Such a high frequency of HCAb secretion cannot fully concur with our current understanding of antibody assembly and secretion. The presence of a large proportion of autoreactive HCAbs in SLE reveals a novel mechanism for the generation of autoreactive antibodies in lupus.

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“…Many kinds of HCAbs have been reported (30)(31)(32)(33). The proportion of HCAbs varies in Camelidae.…”

Section: Discussionmentioning

confidence: 99%

Production of Autoreactive Heavy Chain-Only Antibodies in Systemic Lupus Erythematosus

Yang

Zhuo

et al. 2020

Front. Immunol.

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“…Approximately one third of described γ-HCD develop as a composite lymphoid neoplasm ( 2 , 7 , 10 ). In 2013, Beliauskas et al made a description of 13 cases of HCD, five of which were associated to lymphoproliferative disorders (splenic diffuse red pulp small B-cell lymphoma, splenic marginal-zone lymphoma, mucosa-associated lymphoid tissue (MALT) lymphoma, lymphoplasmacytic lymphoma and monoclonal gammopathy of undetermined significance) ( 2 ).…”

Section: Discussionmentioning

confidence: 99%

“…However, most of the cases described by these authors were associated to autoimmune disease, such as lupus erythematosus, autoimmune thyroiditis and rheumatoid arthritis ( 2 ). In 2016, Iijima et al describe a case of γ-HCD with T-cell large granular lymphocytic leukaemia ( 7 ). They conducted a literature review of composite cases described since 2000.…”

Section: Discussionmentioning

confidence: 99%

“…Aspirate and biopsy specimens may show an increase in plasma cells, lymphocytes, and/or plasmacytoid lymphocytes (similar to the bone-marrow findings in Waldenström macroglobulinemia) ( 3 , 6 ). Nevertheless, in some cases γ-HCD are concurrent with other lymphoid neoplasms, including Hodgkin and non-Hodgkin lymphomas, which usually precede the serologic diagnosis of γ-HCD ( 2 , 7 , 8 ). …”

Section: Introductionmentioning

confidence: 99%

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Gamma heavy-chain disease accompanied with follicular lymphoma: a case report

San-José

Aguadero²,

Perea

et al. 2018

Biochemia Medica

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Heavy chain diseases (HCD) are B-cell lymphoprolipherative disorders characterized by the production of monoclonal heavy chains without associated light chains. Some cases of gamma-HCD (γ-HCD) are concurrent with other lymphoid neoplasm. The monoclonal component is not always detectable by serum electrophoresis, and often an immunofixation procedure is necessary to detect this component. Prognosis is variable, and no established guidelines for follow-up are available. We describe a case of a challenging diagnosis of γ-HCD due to the absence of clinical signs frequently reported in the disease (anaemia and palatal oedema among others). Haematological malignancy was the first suspicion but bone marrow examination was negative. In addition, the presence of an autoimmune bicytopenia and a Klinefelter syndrome complicated the clinical context of the patient. A thoracoabdominal computed tomography reported many small adenopathies whose pathological and immunohystochemical study revealed a follicular lymphoma. Shortly after, serum inmunofixation secondary to an abnormal electrophoretic pattern revealed a gamma paraprotein without light chains. Eventually, γ-HCD in association with follicular lymphoma was the final diagnosis. This is the first case reporting this association.

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“…Patients showed a female predominance (85%) with frequent occurrence of autoimmune disease (69%) [ 8 ]. Iijima et al [ 9 ] report a case γ -HCD and T-cell large granular lymphocytic leukemia. γ -HCD can exist in the absence of clinical symptoms similar to other forms of monoclonal gammopathy of undefined significance (MGUS) [ 10 ].…”

Section: Discussionmentioning

confidence: 99%

Two Cases of γ-Heavy Chain Disease and a Review of the Literature

Ramasamy

Rudzki

2018

Case Reports in Hematology

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Gamma heavy chain disease (γ-HCD) is a rare lymphoproliferative disorder characterised by the production of a truncated immunoglobulin heavy chain. Fewer than 200 cases have been reported in the literature. In some cases, γ-HCD occurs with other lymphoid neoplasms. This study reports clinical, biochemical, haematological, and histological findings in two cases of γ-HCD. We describe newer biochemical diagnostic tools (HevyLite measurement, capillary electrophoresis, and immunotyping) that can aid in the characterisation of γ-HCD. The first case is an 88-year-old woman with γ-HCD. The second case is an 81-year-old woman who developed γ-HCD during treatment for Waldenstrom's macroglobulinemia. In the second patient, histopathology identified a separate clone responsible for the secretion of the gamma heavy chain. Studies on the clonal evolution of the disease may provide insight into therapeutic implications and the genomic complexity of the disease.

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Gamma Heavy Chain Disease with T-cell Large Granular Lymphocytic Leukemia: A Case Report and Review of the Literature

Cited by 6 publications

References 11 publications

Production of Autoreactive Heavy Chain-Only Antibodies in Systemic Lupus Erythematosus

Production of Autoreactive Heavy Chain-Only Antibodies in Systemic Lupus Erythematosus

Gamma heavy-chain disease accompanied with follicular lymphoma: a case report

Two Cases of γ-Heavy Chain Disease and a Review of the Literature

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