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Aim Endometriosis is one of the most common reproductive system diseases, but the mechanisms of disease progression are still unclear. Due to its high recurrence rate, searching for potential therapeutic biomarkers involved in the pathogenesis of endometriosis is an urgent issue. Methods Due to the similarities between endometriosis and ovarian cancer, four endometriosis datasets and one ovarian cancer dataset were downloaded from Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were identified, followed by gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and protein–protein interaction (PPI) analyses. Then, we validated gene expression and performed survival analysis with ovarian serous cystadenocarcinoma (OV) datasets in TCGA/GTEx database, and searched for potential drugs in the Drug-Gene Interaction Database. Finally, we explored the miRNAs of key genes to find biomarkers associated with the recurrence of endometriosis. Results In total, 104 DEGs were identified in the endometriosis datasets, and the main enriched GO functions included cell adhesion, extracellular exosome and actin binding. Fifty DEGs were identified between endometriosis and ovarian cancer datasets including 11 consistently regulated genes, and nine DEGs with significant expression in TCGA/GTEx. Only IGHM had both significant expression and an association with survival, three module DEGs and two significantly expressed DEGs had drug associations, and 10 DEGs had druggability. Conclusions ITGA7, ITGBL1 and SORBS1 may help us understand the invasive nature of endometriosis, and IGHM might be related to recurrence; moreover, these genes all may be potential therapeutic targets.KEY MESSAGEThis manuscript used a bioinformatics approach to find target genes for the treatment of endometriosis.This manuscript used a new approach to find target genes by drawing on common characteristics between ovarian cancer and endometriosis.We screened relevant therapeutic agents for target genes in the drug database, and performed histological validation of target genes with both expression and survival analysis difference in cancer databases.

The prognostic value of current multigene assays for breast cancer is limited to hormone receptor-positive, human epidermal growth factor receptor 2-negative early breast cancer. Despite the prognostic significance of immune response-related genes in breast cancer, immune gene signatures have not been incorporated into most multigene assays. Here, using public gene expression microarray datasets, we classified breast cancer patients into three risk groups according to clinical risk and proliferation risk. We then developed the immune prognostic index based on expression of five immune response-related genes (TRAT1, IL2RB, CTLA4, IGHM and IL21R) and lymph node status to predict the risk of recurrence in the clinical and proliferation high-risk (CPH) group. The 10-year probability of disease-free survival (DFS) or distant metastasis-free survival (DMFS) of patients classified as high risk according to the immune prognostic index was significantly lower than those of patients classified as intermediate or low risk. Multivariate analysis revealed that the index is an independent prognostic factor for DFS or DMFS. Moreover, the C-index revealed that it is superior to clinicopathological variables for predicting prognosis. Its prognostic significance was also validated in independent datasets. The immune prognostic index identified low-risk patients among patients classified as CPH, regardless of the molecular subtype of breast cancer, and may overcome the limitations of current multigene assays.

Heavy chain deposition disease (HCDD) is characterized by the deposition of truncated monoclonal immunoglobulin heavy chains along glomerular basement membranes. Truncated heavy chains are thought to be associated with plasma cell disease (PCD), but previous bone marrow cytology tests showed that only 30% of HCDD cases are related to PCDs. We report the first known use of immunoglobulin heavy chain (IGH) gene rearrangement to diagnose a patient with γ3-HCDD, although bone marrow morphology test identified no abnormalities. Our findings provide strong evidence for a correlation between PCDs and HCDD, which could help understand the genetic background underlying abnormal heavy chains and assess disease prognosis. Further, concordant with previous findings, bortezomib-based chemotherapy had a good therapeutic effect in our patient. We summarize the experience of diagnosing and treating a case of HCDD, and combine this with a literature review to further explore the correlation between PCDs and HCDD, which has important clinical value.

Gamma-heavy chain disease is a rare disease, described so far in approximately 150 cases. The aim of this work was laboratory dia-gnostics of immunoglobulin heavy chain disease.A 60-year-old patient was referred to the University Hospital in Ostrava for suspected marginal zone lymphoma from gastric bio-psy. Staging examinations including bone marrow trepanobio-psy and PET/CT were added; special examinations required serum protein electrophoresis, immunofixation electrophoresis, determination of polyclonal immunoglobulins, free light chains, and immunoglobulin heavy/light chain pairs. Isoelectric focusing in agarose gel followed by affinity immunoblotting and SDS electrophoresis was added due to unclear findings.0.1 % of plasma cells were found in the bone marrow, of which 87 % were clonal (pathological) plasma cells, followed by the cyt cytotype LAMBDA + CD38 + CD138 + CD45 + CD19 + CD56- CD27 + CD81- CD117-. Monoclonal heavy chains were found in the patients serum. No monoclonal immunoglobulin heavy or light chains were detected in urine. The PET/CT examination showed generalized lymphadenopathy, splenomegaly and inhomogeneous accumulation of fluorodeoxyglucose in axillary and appendicular skeleton, but without the presence of typical osteolytic lesions.Monoclonal heavy chains of immunoglobulins are a rare disease. In contrast to the detection of a complete paraprotein molecule, additional methods must be used to confirm them. The finding of monoclonal heavy chain gamma in the serum of the study patient is related to the presence of marginal zone lymphoma, which was proven from a gastric bio-psy. The study was supported by the project of MH CZ - DRO - FNOs /2017 (Biobank in Teaching Hospital Ostrava) The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.

Introduction. Heavy-chain diseases (HCDs) are rare B-cell lymphoproliferative diseases that do not have a classical clinical picture. A characteristic feature of this disease is the secretion of fragmented heavy chains of various immunoglobulin isotypes. Currently, there are four known variants of this disease: μ, γ, α, and δ.Aim. To describe the clinical observation of μ-HCD, hidden under the mask of systemic amyloidosis, and the associated diffi culties of primary diagnosis.Main Findings. A rare clinical case of μ-HCD in combination with systemic amyloidosis (light chain amyloidosis-AL), transthyretin amyloidosis (transthyretin amyloidosis-ATTR), and non-amyloid deposits in a 64-year-old patient is presented. The severity of the condition was due to the clinical picture of chronic heart failure, polyneuropathy. Upon examination, Waldenstrom’s macroglobulinemia was diagnosed while a diagnosis of amyloidosis was not established. Immuno-chemotherapy was performed under the RB program (rituximab and bendamustine). The effect of the therapy was minimal and short-term. The patient’s condition progressively worsened, and the patient died due to acute cardiovascular failure. The main diagnosis was revised in favor of μ-HCD. The autopsy revealed widespread amyloid and non-amyloid lesions of organs and tissues. Conflict of interest: the authors declare no conflict of interestFinancial disclosure: the study had no sponsorship

Rationale & Objective Heavy chain deposition disease (HCDD) is a rare consequence of monoclonal immunoglobulin deposition disease that has not been well characterized in non-white populations. To explore the clinicopathologic characteristics and outcomes of HCDD in Chinese individuals, we report on a case series assembled in a single center in China. Study Design Case series. Setting & Participants 25 patients with biopsy-proven HCDD were studied retrospectively. Results 14 men and 11 women with an average age of 50.3 years were studied. The patients presented with hypertension (76%), edema (96%), anemia (84%), serum creatinine level > 1.2mg/dL (68%), nephrotic-range proteinuria (56%), and microscopic hematuria (80%). One (4%) patient had multiple myeloma diagnosed. Serum immunofixation electrophoresis showed that 10 of 21 (48%) patients were positive for monoclonal immunoglobulin. Hypocomplementemia of C3 was found in 68% of patients. Nodular mesangial sclerosis was identified in all patients by using light microscopy. Using immunofluorescence, all 25 patients had deposition of heavy chains of immunoglobulin G class (γ1, 13; γ2, 2; γ3, 6; γ4, 2; γ1 and γ4, 1; and γ2 and γ4, 1). During an average of 40.1 months of follow-up of 20 patients, 65% had improved kidney function, 10% had worsening kidney function, and 25% progressed to kidney failure. Mean values for kidney and patient survival were 37.8 and 40.1 months, respectively. Kidney survival was higher among patients who received chemotherapy. Limitations Retrospective study, single-center experience. Conclusions In this case series of HCDD in a single center in China, the heavy chain deposits seen in the kidney biopies of all individuals were of immunoglobulin G class. Chemotherapy improved kidney function, especially among individuals in an early stage of the disease.

We describe the use of MALDI-TOF mass spectrometry in the analysis of a suspected case of gamma heavy chain disease. The patient had an abnormal serum immunofixation result where a monoclonal gamma heavy chain band was present without a corresponding light chain. Analysis by MALDI-TOF mass spectrometry revealed large peaks in the spectrum following IgG-specific purification. The m/z values of the peaks were outside the expected range for normal heavy chains or light chains. Corresponding peaks were not present in mass spectra of the kappa- or lambda-specific purifications. MALDI-TOF MS confirmed the presence of a truncated heavy chain without associated light chains. This case report demonstrates the value of mass spectrometry in interpreting challenging cases such as the identification of heavy chain disease.

Mu heavy chain disease is a rare lymphoid neoplasm characterized by vacuolated bone marrow plasma cells and secretion of defective mu immunoglobulin heavy chains. The biological basis of mu heavy chain disease is poorly understood.We report a case of mu heavy chain disease with MYD88 L265P mutation and deletion of 6q, genetic aberrations that are both strongly associated with lymphoplasmacytic lymphoma/Waldenström macroglobulinemia. Identification of the truncated mu immunoglobulin was facilitated by mass spectrometric analysis of the patient's serum.Mu heavy chain disease has been described as similar to chronic lymphocytic leukemia; however, the frequency of lymphocytosis in mu heavy chain disease has not been previously reported. We reviewed all previously published mu heavy chain disease reports and found that lymphocytosis is uncommon in the entity. This finding, along with the emerging genetic feature of recurrent MYD88 mutation in mu heavy chain disease, argues that at least a significant subset of cases are more similar to lymphoplasmacytic lymphoma than to chronic lymphocytic leukemia.

Heavy chain diseases are rare gammopathies characterized by the production of a truncated heavy chain monoclonal immunoglobulin without associated light chain. These hemopathies, which are frequently associated with immunological or hematological disorders, are clinically closer to lymphomas than to myelomas. The case that we report illustrates the difficulty to characterize a heavy chain gammopathy discovered in an elderly woman admitted in the department of internal medicine for alteration of general condition.

Primary agammaglobulinemia result from specific alterations in B cells, which lead to low antibody production. Diagnostic suspicion is established with a history of repeated infections, low immunoglobulins, and absence of CD19+ B lymphocytes. The diagnosis is confirmed by genetic analysis and the detection of a mutation linked to the X or autosomal recessive or dominant chromosome. In Peru, there is no literature on primary agammaglobulinemia and no reports on the genotype of patients with suspected primary agammaglobulinemia. Under this scenario, a study was performed to describe the genotype of patients with suspected primary agammaglobulinemia. Twenty (20) patients were found with mutations in the BTK gene and an autosomal recessive IGHM mutation. Thirteen (13) hereditary mutations and seven de novo mutations were found. It is concluded that the group of primary agammaglobulinemia are mostly mutations in the BTK gene, corresponding to X-linked agammaglobulinemia.Las agammaglobulinemias primarias (AP) resultan de alteraciones específicas en las células B, lo cual, conduce a baja producción de anticuerpos. La sospecha diagnóstica se establece con el antecedente de infecciones a repetición, inmunoglobulinas bajas y la ausencia linfocitos B CD19+. El diagnóstico se confirma mediante el análisis genético y la detección de una mutación ligada en el cromosoma X o autosómico recesiva o dominante. En Perú, no hay literatura sobre AP ni reportes sobre el genotipo de los pacientes con sospecha de AP. Bajo este escenario, se realizó un estudio que describió el genotipo de pacientes con sospecha de AP. Se encontraron 20 pacientes con mutaciones en el gen BTK y una mutación autosómica recesiva IGHM. Se hallaron 13 mutaciones hereditarias y siete mutaciones de novo. Se concluye que las AP son, en su mayoría, mutaciones en el gen BTK que corresponden con AP ligadas al cromosoma X.

Background Gamma heavy chain disease (γ-HCD) is a monoclonal gammopathy defined by an abnormal clonal and isolated production of incomplete heavy chain gamma (γ), unable to bind with light chains kappa or lambda. This disease is rare and remains poorly described. Its association to lymphoid neoplasm is well established, but exceptional forms of γ-HCD may also accompany auto-immune diseases. We report here a new case of γ-HCD characterized by an indolent course with a 4-year follow-up, and its association with quiescent rheumatoid arthritis (RA). Case presentation We report the case of a 85-year old French white man followed for quiescent anti-CCP+ rheumatoid arthritis treated by prednisolone 4 mg/day and hydroxychloroquine 200 mg/day since 10 years, and a monoclonal gammopathy of undetermined significance for 6 years, who was hospitalized for costal fractures after a fall. Serum protein electrophoresis showed a stable small monoclonal peak, and capillary electrophoresis/immunosubtraction technique identified an isolated clonal γ-heavy chain (HC). Bone marrow aspiration was normal and he had no other lymphoproliferation. The monoclonal peak remained stable after 4 years of follow-up. Conclusions In case of monoclonal peak without complete monoclonal Ig on serum protein electrophoresis, the diagnosis of γ-HCD should be discussed and capillary electrophoresis/immune-subtraction is a mean to detect isolated monoclonal heavy chain (HC). Gamma-HC disease is rare, may be associated to RA, and may have an indolent course.

Heavy chain disease is a rare entity characterized by the production of incomplete immunoglobulin heavy chain without associated light chain. It is a B-cell lymphoproliferation, categorized according to the immunoglobulin involved. It is often associated with lymphomas but also with autoimmune diseases.We report the case of a 70-year-old patient who presented a gamma-type heavy chain disease, associated with a diffuse large B-cell lymphoma in the context of myelodysplastic syndrome.This is the first case of diffuse large B-cell lymphoma associated gamma heavy chain disease described in the context of myelodysplastic syndrome.

Background Gamma heavy chain disease is a disorder characterized by the production of truncated heavy chains without associated light chains. Clinical manifestations differ greatly. Thus far no standard treatment has been formulated. Methods We report a case of Franklin's disease, which proved diagnostically challenging due to the absence of symptoms and disorders frequently associated with the disease. Results Standard screening tests for monoclonal gammopathy remained unremarkable. Serum immunofixation detected monoclonal truncated gamma heavy chains. Conclusions Serum immunofixation should be performed, if heavy chain disease is strongly suspected. Flow cytometry and genetic evaluation are needed to provide additional insights into Franklin's disease.

Heavy chain disorders are rare B-cell disorders and include heavy chain disease, heavy chain deposition disease, and heavy chain amyloidosis. These disorders share the pathognomonic finding of a truncated immunoglobulin heavy chain without an associated light chain in the serum or urine in the case of heavy chain disease or in the tissues in the case of heavy chain deposition disease and heavy chain amyloidosis but are clinically distinct entities. The clinical recognition and systematic approaches to these disorders are challenging because of the rarity of the diseases, lack of consensus on treatment approaches, and minimal data with novel therapy. Herein we present a review of the literature and 5 consecutive cases at a single institution of gamma heavy chain disease and heavy chain deposition disease treated with novel agents including regimens of CRd (cyclophosphamide, lenalidomide, and dexamethasone), CyBorD (cyclophosphamide, bortezomib, and dexamethasone), R-CVP (rituximab, cyclophosphamide, vincristine, and dexamethasone), BR (bendamustine and rituximab), V-EPOCH (bortezomib, etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin), and autologous hematopoietic stem cell transplantation.

Heavy-chain deposition disease (HCDD) is characterized by tissue deposits of a truncated monoclonal immunoglobulin heavy-chain (HC) on basement membranes. Diagnosis is usually made on kidney biopsy, showing nodular glomerulosclerosis with HC deposits which can be missed, resulting in delay in diagnosis. We report four γ1-HCDD patients presenting with cutis laxa, hypocomplementemia and hypoalbuminemia. In two patients, unsuspected HCDD was revealed by cutis laxa and diagnosis was made on skin biopsy. In all patients, serum albumin and complement represented surrogate markers for disease monitoring. In γ-HCDD, extrarenal manifestations such as cutis laxa may precede renal injury and are precious tools for an early diagnosis, which is crucial to avoid progression of irreversible renal and elastic tissue damage.

Although gamma heavy chain disease (γ-HCD) lesions occasionally morphologically resemble angioimmunoblastic T-cell lymphoma (AITL), no association has been described in detail due to the rarity of the disease. In this report, we present a rare manifestation of methotrexate (MTX)-associated lymphoproliferative disorders (LPDs) with AITL-like features accompanied by γ-HCD in a 75-year-old man with rheumatoid arthritis (RA). A biopsy specimen was evaluated using immunohistochemistry, clonal analyses of immunoglobulin VH and T-cell receptor γ gene rearrangements by polymerase chain reaction, and Sanger sequencing for confirmation of the structure of deleted γ-HCD clones. The histological features characterized by proliferation of CD4- and PD-1-positive medium-sized T cells and arborizing high endothelial venules together with numbers of small lymphocytes, eosinophils, plasma cells, and histiocytes in the background mimicked those of AITL, but did not completely fulfill the diagnostic criteria. Clonal analysis demonstrated that the specimen contained multiple LPDs of both B-cell and T-cell lineages. Sequence analysis confirmed the co-existence of a clone responsible for production of the abnormal heavy chain. This report provides new insights into the pathology of γ-HCD. Multiple host-derived factors (e.g., RA and/or use of MTX) may be responsible for the occurrence of LPDs of multiple lineages within a single lymph node.

BACKGROUND Heavy chain diseases (HCDs) are B-cell neoplasms characterised by production of monoclonal (M) protein consisting only of immunoglobulin heavy chain without a bound light chain. Three types have been recognized- IgA alpha HCD (most common, a form of extra nodal marginal zone lymphoma of mucosal associated lymphoid tissue aka immunoproliferative small intestinal disease [IPSID], Mediterranean lymphoma or Seligmann disease], IgG gamma HCD (aka Franklin's disease, variant of lymphoplasmacytic lymphoma) and IgM mu HCD (rarest, resembles chronic lymphocytic leukemia). Limited data is available regarding the epidemiology, survival patterns, and incidence of second primary malignancies in patients with HCD in the Unites States. MATERIALS AND METHODS We performed a retrospective analysis using SEER* stat version 8.3.9 statistical software and November 2020 submission of SEER 18 registry which covers ~ 27.8 % of US population based on the 2010 census. We identified all cases > 1 years old diagnosed with Heavy chain disease between 2000 and 2018 using International Classification of Diseases for Oncology edition 3 (ICD-O-3) code 9762/3. We analyzed survival using Kaplan- Meier method, and MP-SIR session was used to calculate the risk of second primary malignancy. RESULTS A total of 64 cases of HCD were identified. Most common primary sites of involvement were bone marrow (82.8%), lymph nodes (9.3%), GI tract (3.1%), others (4.6%)- spleen, blood and vertebral column. The crude, age-adjusted to 2000 US standard population and age-specific incidence rate of HCD in the United States is < 1/100,000 respectively. The median age at diagnosis is 68 years with incidence in males being about 1.3 times that of females. Bimodal age distribution was observed, with peak incidence between ages 60-64 and 75-79 [Figure 1]. In our entire cohort, 82.8% (n=53) patients were Caucasians, 15.6 % (n=10) patients were African Americans, and 1.5% (n=1) patients were American Indian/Alaska Native. Among Caucasians, 56.6% (n=30) patients were males, and 43.3% (n=23) patients were females. Between 2000-2018, the maximum cases (n=7 each) were diagnosed in the year 2002 and 2008 [Figure 2] The median overall survival for the entire cohort was 48 months (95% CI: 35- 61). Overall survival rates of all ages, sex and race at 1 year, 2 year and 5 years were found to be 86.1%, 71.4%, 57.8% respectively. OS at 5 years declines after 70 years .Patients with HCD are at risk of developing subsequent solid and haematological malignancies within 5 years of diagnosis. 9 (14 %) cases developed SPMs: urinary bladder (n=1), lung and bronchus (n=2), Hodgkin-nodal (n=1), Non-Hodgkin Lymphoma -extra nodal (n=1), GI cancers [stomach (n=1), esophagus (n=1) and ascending colon (n=1)], miscellaneous (n=1). [Figure 4]. The mean follow-up duration for new SPM was 51 months. Overall, 39 patients died: 3 (4%) from miscellaneous malignant cancer and 11 (17%) patients from haematological malignancy; the most common being Non-Hodgkin lymphoma (n=8), followed by Hodgkin lymphoma (n=1), Multiple myeloma (n=1) and leukemia (n=1). CONCLUSIONS HCD is an extremely rare haematological malignancy. The incidence of HCD is proportionately higher among Caucasians as compared to other races, with no reported case among Asian or Pacific Islanders. Among Caucasians, males and females have approximately equal risk of acquiring HCD. Most patient die because of their primary haematological malignancy. We recommend close follow-up for at least the first 5 years after initial diagnosis. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Heavy Chain Disease (HCD) is a group of rare B-cell proliferative disorders. Diagnosis depends on the detection of a truncated heavy chain with no associated light chain, often done by serum or urine immunofixation. This approach has been reported to have low specificity, since associated light chain bands are sometimes not visible and heavy chain bands can be mistaken for polyclonal bands. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) offers improved sensitivity in detecting monoclonal immunoglobulins. Truncation is thought to happen in the constant heavy chain (CH1) region, detected as a fragment of mass 27,000 Da on MALDI-TOF. Other mass patterns have not been reported in the literature. In this study, frozen serum samples from 8 heavy chain disease patients were analyzed by MALDI-TOF mass spectrometry. Spectra were reviewed on Mass-Fix software and visually inspected for monoclonal peaks. We detected two types of patterns for the IgG heavy chain disease. One pattern shows an IgG heavy chain with truncated mass (27,000 Da vs. 50,000 Da) and another in which the mass of the IgG heavy chain is greater than normal (65,000 Da). Follow-up work demonstrates that these are most likely dimers of truncated heavy chains. Thus, mass spectrometry-based immunofixation can provide new insights into heavy chain disease biology, mechanism, and progression, which are not identified by traditional diagnostic methods.

Protein biomarkers for epithelial ovarian cancer are critical for the early detection of the cancer to improve patient prognosis and for the clinical management of the disease to monitor treatment response and to detect recurrences. Unfortunately, the discovery of protein biomarkers is hampered by the limited availability of reliable and sensitive assays needed for the reproducible quantification of proteins in complex biological matrices such as blood plasma. In recent years, targeted mass spectrometry, exemplified by selected reaction monitoring (SRM) has emerged as a method, capable of overcoming this limitation. Here, we present a comprehensive SRM-based strategy for developing plasma-based protein biomarkers for epithelial ovarian cancer and illustrate how the SRM platform, when combined with rigorous experimental design and statistical analysis, can result in detection of predictive analytes. Our biomarker development strategy first involved a discovery-driven proteomic effort to derive potential N-glycoprotein biomarker candidates for plasma-based detection of human ovarian cancer from a genetically engineered mouse model of endometrioid ovarian cancer, which accurately recapitulates the human disease. Next, 65 candidate markers selected from proteins of different abundance in the discovery dataset were reproducibly quantified with SRM assays across a large cohort of over 200 plasma samples from ovarian cancer patients and healthy controls. Finally, these measurements were used to derive a 5-protein signature for distinguishing individuals with epithelial ovarian cancer from healthy controls. The sensitivity of the candidate biomarker signature in combination with CA125 ELISA-based measurements currently used in clinic, exceeded that of CA125 ELISA-based measurements alone. The SRM-based strategy in this study is broadly applicable. It can be used in any study that requires accurate and reproducible quantification of selected proteins in a high-throughput and multiplexed fashion.

[Figure][1] A 78-year-old woman from Sudan with presumed tuberculous lymphadenitis without preexisting autoimmune disease presented with fatigue, persistent fever, hepatosplenomegaly, and generalized lymphadenopathy. Inguinal lymph node biopsy showed a diffuse neoplasm with plasmacytic

In this chapter, the discussion will be primarily be focused on challenges in interpretation of various tests performed for detection of monoclonal gammopathy (monoclonal protein), cerebrospinal fluid (CSF) electrophoresis, as well as autoimmune serology. A monoclonal protein (paraprotein, M protein) is a monoclonal immunoglobulin that is secreted by an abnormal clone of plasma cells. The M protein can be an intact immunoglobulin, only light chains (light chain myeloma, light chain deposition disease or AL amyloidosis), or rarely only heavy chains (heavy chain disease). Correct diagnosis of monoclonal gammopathy is very important because it is linked to multiple myeloma. Sources of errors in testing for these analytes will be discussed with an emphasis on minimizing or eliminating interferences.

Heavy chain diseases (HCDs) are rare B cell lymphoplasma cell proliferative disorders that are characterized by the production of incomplete monoclonal immunoglobulin (Ig) heavy chains without the associated light chains. γ-HCD (IgG subtype) is a rare subtype, with ~150 cases reported in the literature to date; however, to the best of our knowledge, no reports of T cell receptor (TCR) gene rearrangement in γ-HCD exist in the literature. The present study reports the case of an 81-year-old man with γ-heavy chain disease associated with TCR gene rearrangement, identified in lymph node biopsy and bone marrow aspirate specimens. The present case revealed an alternative manifestation of γ-HCD, which may provide additional biological insights into this rare B cell disorder.

Heavy chain deposition disease is defined by the presence of tissue deposits of truncated monoclonal Ig heavy chains, usually associated with an underlying plasma cell clone. In this issue of Kidney International , Bridoux et al. described the clinical, histologic, and molecular characterization of 15 patients with heavy chain deposition disease, which is the largest case series to date. Notable findings included the frequent presence of C3 deposits and hypocomplementemia, the uniform finding of truncated heavy chains with the deletion in the heavy chain constant region 1, and the common occurrence of an abnormal serum-free κ:λ ratio, despite the absence of light-chain tissue deposition. Importantly, this study showed that clinical outcomes are improved significantly with modern antiplasma cell therapies such as bortezomib.