Heavy Chain Deposition Disease Research Articles

Bilateral sequential ischemic retinopathy and optic neuropathy in IgG1 heavy chain deposition disease.

To report a case of progressive ischemic retinopathy and optic neuropathy in a patient with heavy chain deposition disease (HCDD), a rare form of monoclonal immunoglobulin deposition disease (MIDD). Our case describes a 74-year-old woman diagnosed with IgG1 lambda HCDD. After treatment with daratumumab and intravenous IVIG therapy, the patient developed worsening ischemic retinopathy and optic neuropathy, neovascular glaucoma, and bilateral sequential vitreous hemorrhages, necessitating surgical intervention. We present multimodal imaging from the onset of ischemic retinopathy to end-stage maculopathy illustrated by optical coherence tomography (OCT) angiography. Despite discontinuing treatment with daratumumab and providing maximal ocular interventions to control the complications of neovascular disease, the patient's condition progressed, resulting in profound vision loss. Our case illustrates the potential for HCDD to cause end-organ disease, including ischemic retinopathy and optic neuropathy, possibly worsened by the patient's underlying cardiovascular risk factor status and medications. Daratumumab, a humanized IgG1 kappa monoclonal antibody that binds to CD38 used to treat specific blood cancers, has been reported to cause disturbances in retinal blood flow, including retinal artery and vein occlusions. It remains to be determined whether careful patient selection or dose adjustments and timing of HCDD treatments could protect vision by reducing the risk of these rare yet severe ocular complications.

Primary adrenal insufficiency developed 22 years after the diagnosis of light and heavy chain deposition disease: a case report.

Monoclonal immunoglobulin deposition diseases (MIDDs), including light and heavy chain deposition disease (LHCDD), are rare and heterogeneous disorders associated with underlying B-cell clonal disorders. Adrenal involvement is a potential extrarenal manifestation of MIDDs; however, limited data are available regarding its prevalence and clinical presentation. Herein, the present report describes, for the first time, a case of primary adrenal insufficiency that developed twenty-two years after a diagnosis of LHCDD had been made. A 69year-old woman with a 10year history of hemodialysis suddenly became bedridden after falling down stairs in the absence of focal neurological deficits. Subsequently, she experienced appetite loss, nausea, vomiting, a fever of unknown origin, and unexplained hypotension. Several months later, primary adrenal insufficiency and normal pressure hydrocephalus were diagnosed and successfully managed. The long-term clinical prognosis of MIDDs has not been fully elucidated despite recent advances in the management of the disorders. This report may contribute to improving our understanding of the disease course.

A Study of Nodular Glomerulopathy – A Single-center Experience and Review

ABSTRACT Background: Mesangial expansion is a histopathological manifestation characterized by abnormal proliferation of mesangial cells and accumulation of matrix proteins within the central region of the glomerulus. While diabetes is a well-known cause of mesangial expansion, several rare diseases can also present with this pathology. This study aimed to estimate the prevalence of lesions exhibiting mesangial expansion in a tertiary care center in Tirunelveli, India, and elucidate the spectrum of disorders contributing to mesangial expansion lesions in renal biopsies. Methodology: A retrospective analysis of renal biopsies conducted at Tirunelveli Medical College and Hospital from 2016 to 2022 was performed. Kidney tissue samples were subjected to light microscopy and immunofluorescence studies using appropriate stains. Patients with isolated mesangial expansion were identified. Demographic details, clinical indications for biopsy, and pathological findings were recorded and analyzed. Results: Out of 616 kidney biopsies, mesangial expansion was present in 39 patients (6.33%). Notably, nodular mesangial expansion was observed in 33 patients (5.3%), with diabetes being the most prevalent associated condition (74.19%). Amyloidosis, heavy chain deposition disease, fibrillary glomerulonephritis, collagen fibrotic glomerulopathy, and idiopathic nodular glomerulosclerosis were identified as other contributors to mesangial expansion. Glomerular filtration rate and interstitial fibrosis and tubular atrophy were worse in the diabetic population. Conclusions: This study sheds light on the varied etiologies contributing to mesangial expansion beyond diabetes, emphasizing the importance of specialized staining methods for precise diagnosis.

One Case of Heavy Chain Deposition Disease Treated with Dara+KD Regimen and Literature Review

Background: Heavy chain deposition disease (HCDD) is a systemic disease caused by the deposition of monoclonal immunoglobulin heavy chains in tissues.It is a rare monoclonal immunoglobulin deposition disease. The mechanism of HCDD is still unclear, which may be related to the deletion of heavy chain constant region 1 and the activation of the Complement system by monoclonal heavy chains. Renal biopsy remains the gold standard for diagnosing HCDD at present. There are significant individual differences in the formation of abnormal heavy chains in HCDD patients, and FLC, M protein, and complement detection have certain reference significance for the evaluation of diagnosis and treatment processes. The chemotherapy scheme represented by Bortezomib has a certain effect. HDM/ASCT and kidney transplantation can be used as second-line treatment for some patients. At present, there is no report on the use of CD38 monoclonal antibody combined with KD regimen. Objective: To explore the efficacy and toxicity of CD38 monoclonal antibody combined with KD regimen in the treatment of heavy chain deposition disease. Methods: The diagnosis, treatment and efficacy of HCDD who hospitalized in the Hematology Department of the First Affiliated Hospital of Sun Yat-sen University was analyzed, and the value of CD38 monoclonal antibody combined with KD regimen in the treatment of HCDD was discussed. The patient was male, 44 years old, due to “depressed edema of both lower limbs and eyelid edema for more than two months”. Results: Heavy chain deposition disease is a rare malignant Plasma cell disease. CD38 monoclonal antibody combined with KD regimen can rapidly alleviate the disease,.This patient got CR and obvious improvement of clinical symptoms after 1 cycle chemotherapy, and has no obvious side effects.We be expected to do 4 cycle chemothetaphy and would do ASCT.until now,this patient has got 3 cycles. Conclusion: Heavy chain deposition disease is a rare malignant Plasma cell disease. CD38 monoclonal antibody combined with KD regimen can rapidly alleviate the disease, with fast onset time, high CR rate, obvious improvement of clinical symptoms, and no obvious side effects.

Light and heavy chain deposition disease with focal amyloid deposition diagnosed with mass spectrometry: a case report

BackgroundLight and heavy chain deposition disease (LHCDD) is a rare condition characterised by the deposition of immunoglobulin components in the kidneys. Similarly, Amyloidosis is also caused by the deposition of light chain and/or heavy chain components of immunoglobulins which are folded into amyloid fibrils characterised by Congophilic deposits that exhibit apple-green birefringence under polarised light. Only a handful of reports describing LHCDD with amyloid fibril deposition have been previously published, however, none have characterized the composition of the deposited immunoglobulin components via mass spectrometry.Case presentationWe report a case of a 79-year-old Japanese woman with nephrotic syndrome. Bone marrow aspiration revealed a slight proliferation of plasma cells (under 10%). Immunofluorescence assessment of renal biopsy showed amyloid-like deposits in the glomerulus that were positive for IgA and kappa. Further, the Congo red staining of the deposits was faintly positive, and only a slight birefringence was detected. Electron microscopy confirmed fine fibrillar structures and non-amyloid deposits. Finally, mass spectrometry revealed that the deposits were composed of abundant amounts of light chain with small amounts of heavy chain. Therefore, the patient was diagnosed with LHCDD and focal amyloid deposition. Chemotherapy was subsequently initiated, which resulted in haematological and renal response. Under polarised light, faint birefringence with Congo red staining and periodic acid-methenamine silver positivity indicated that the deposits were mostly non-amyloid fibrils with a small component of amyloid fibrils. Generally, the diagnosis of heavy- and light-chain amyloidosis is defined by greater heavy chain deposition compared to the light chain. However, in our case, contrary to the definition, the light-chain deposition was far greater than that of the heavy-chain.ConclusionsThis is the first case of LHCDD with focal amyloid deposition diagnosed by analysing the glomerular deposits by mass spectrometry.

#3922 CLINICOPATHOLOGICAL CHARACTERISTICS OF LIGHT AND HEAVY CHAIN DEPOSITION DISEASE: A CASE SERIES FROM A SINGLE CENTER

Abstract Background and Aims Light and heavy chain deposition disease (LHCDD) is the rarest form of monoclonal immunoglobulin deposition disease (MIDD) characterized by the deposition of the monoclonal light chain and heavy chain. At present, the large-scale clinical research data of LHCDD is limited. We explore the clinical-pathologic characteristics and outcome of LHCDD in a single center of China, to obtain a better understanding of this disease. Method We reviewed 65291 native kidney biopsies from January 2008 to December 2022. Ten patients with biopsy-proven LHCDD diagnosed were studies retrospectively. Results 4 males and 6 females, with an average age of 52.5 ± 8.9 years were enrolled. The patients were presented with hypertension (80%), anemia (90%), elevated serum creatinine (70%), proteinuria (100%), nephrotic syndrome (30%) and microscopic hematuria (90%). Serum immunofixation electrophoresis showed that 8 (80%) patients were positive for monoclonal immunoglobulin (IgG-κ/IgG-λ/IgA-λ: 3/2/3). Serum free light chain (FLC) ratio was abnormal in 9 (90%) patients. Among them, 5 patients had an Elevated FLC ratio (κ:λ > 1.65), and an FLC ratio < 0.26 was observed in 4 patients. Two patients were diagnosed with multiple myeloma. Histologically, nodular mesangial sclerosis was identified in 9 (90%) patients. Immunofluorescence showed that 6 patientshad depositions of heavy chain IgG (γ1-κ/γ1-λ/γ2-κ/γ2-λ/γ3-κ:2/1/1/1/1), and 4 patients of heavy chain IgA (α-κ/α-λ:1/3). During a median of 28 months of follow-up (range, 6–104 months) in 9 patients, 8 patients received chemotherapy. Three (33%) patients had complete hematologic remission (CR), 2 (22%) had very good partial hematologic response (VGPR) or partial hematologic response (PR), and 4 (44%) had no response (NR). One (11%) had stable/improved renal function, 6 (67%) had worsening renal function, and 3 (33%) progressed to ESRD. All 9 patients survived. Conclusion In this case series of LHCDD in a single center in China, light and heavy chain deposition in renal tissues was most frequent with IgG-κ, followed by IgA-λ, IgG-λ and IgA-κ. More than half patients had hematologic response but poor renal prognosis.

Prevalence of MGCS Among Patients With Monoclonal Gammopathies.

Prevalence of MGCS Among Patients With Monoclonal Gammopathies.

Heavy chain deposition disease (HCDD) of the kidney in a patient of treated chronic myeloid leukemia with imatinib

Chronic myeloid leukemia is a clonal disorder of myeloid origin which transforms into more aggressive phenotypes, either acute myeloid leukemia or acute lymphoblastic leukemia. The long-term outcome of chronic myeloid leukemia has significantly improved with tyrosine kinase inhibitor imatinib. In contrast, heavy chain deposition disease is a disorder of lymphoid origin due to a plasma cell clone classified under monoclonal immunoglobulin deposition disease with truncated monoclonal heavy chain deposition along basement membranes of many organs, predominantly the kidneys causing significant organ dysfunction. The connection between the two disorders seems to be vague and undefined. We report a novel case of treated chronic myeloid leukemia with imatinib in sustained clinical and cytogenetic remission who presented with heavy chain deposition disease of the kidney, causing renal dysfunction and nephrotic range proteinuria that responded to clone-directed therapy. Given these disorders’ two different cell lines, their association could be fortuitous only. However, in the light of a few dozen cases published thus far in which the prototypical plasma cell disorders multiple myeloma and monoclonal gammopathy of undetermined significance have evolved from cases of treated CML, this association seems to be genuine, the possible genesis of which is discussed in this manuscript. Long-term exposure of chronic myeloid leukemia patients to imatinib could predispose some rare, vulnerable patients to a plasma cell disorder, including heavy chain deposition disease.

Outcomes in Patients with Renal Monoclonal Immunoglobulin Deposition Disease

BACKGROUND: Monoclonal immunoglobulin deposition disease (MIDD) is characterized by the production of abnormal monoclonal immunoglobulins that deposit in the kidney and other organs. MIDD causes proteinuria, renal damage and eventually renal failure. Currently, there are few studies on the outcomes of patients (pts) with renal MIDD (R-MIDD). METHODS: We performed a single-center retrospective analysis on patients that were seen at the University of California San Francisco Hematology clinic for MIDD from 2010 to 2020. All pts must have had biopsy-proven R-MIDD. Demographic and disease-related characteristics at diagnosis were collected as well therapies administered. Diagnosis of multiple myeloma was per IMWG criteria (Rajkumar et al. Lancet Oncology 2014). Hematologic response and renal response were assessed per previously published criteria (Palladini et al. J Clin Oncol 2012; Palladini et al. Blood 2014). Overall survival (OS), time-to-next treatment (TTNT), time-to-renal progression (TTRP), time-to-dialysis (TTD) were estimated using the Kaplan-Meier method. TTRP was defined as time from the start of treatment to renal progression censored by last follow-up or date of renal transplant. TTD was defined as time from start of treatment to dialysis or last follow-up. Pts already on dialysis at diagnosis were excluded from TTRP and TTD. RESULTS: Thirty-four pts with R-MIDD were identified, 31 light chain deposition disease, 2 heavy chain deposition disease and 1 light and heavy chain deposition disease. Median age at diagnosis was 63 (IQR 58-70) with 13 (38.2%) females. Median creatinine and estimated GFR at diagnosis were 2.80 mg/dL (IQR 3.17-5.57) and 25 ml/min/1.73m2 (IQR 13-40) respectively. Median involved free light chain (FLC) was 819 mg/L (IQR 130-2870), and difference in FLC 433 mg/L (IQR 85-1022). All pts had abnormal serum free light chains and 25 (73.5%) pts had kappa R-MIDD. Median bone marrow plasma cells percentage was 19% (IQR 10-38%). The most common cytogenetic abnormality was del 13 in 6/25 pts (24.0%). A concurrent diagnosis of myeloma was presented in 10 (32.3%) pts. Pts underwent a median of 2 lines of treatment (IQR 1-2). Median follow-up was 5.95 years (range 0.27 - 22.3 years). Pts were treated at induction with the following therapies: Group 1) immunomodulatory drug (IMiD) +/- bortezomib (Bor) (8/34, 23.5%); Group 2) Bor without IMiD (24/34, 70.6%) or Group 3) other (2/34, 5.9%). Autologous stem cell transplant (ASCT) was performed in 82.4% of pts. The 3- and 6-month hematologic response of ≥VGPR was 30.4% (7/23) and 55.6% (15/27) respectively. At the 6-month, Group 1, 2 and 3 had a ≥VGPR of 14.3%, 26.3% and 100% respectively though Group 3 only had 2 pts. Of the 29 pts assessed for best renal response, 9 pts (31.0%) had a renal response. Best renal response for group 1, 2, and 3 occurred in 0%, 38.1% and 100% of pts, respectively. Median TTNT was 2.9 years. Of 34 pts, only 5 died and median overall survival was not reached (Fig.1A). Improved median OS was associated with diagnosis after 2010 v ≤2010 (p=0.1) (Fig. 1B), >60 years old at diagnosis v ≤60 (p=0.1) (Fig. 1C) and treatment with ASCT (p=0.058) (Fig. 1D), though none met statistical significance. Renal progression occurred in 63.3% pts with median TTRP of 1.8 years. Dialysis dependence occurred in 33.3% pts with median TTD not reached (Fig. 2A). TTD did not differ significantly for pts diagnosed >2010 v ≤2010 (p=0.9) (Fig. 2B), ASCT (p=0.7) (Fig. 2D) though was better for pts who were diagnosed >age 60 vs ≤60 (p=0.027) (Fig. 2C). Five pts had a renal allograft, 3 of whom received the allograft after chemotherapy initiation, with 1 graft failure. In a landmark analysis at 6 months, OS and TTRP was better in pts with ≥VGPR compared to <VGPR, though both did not meet statistical significance (p=0.3 and p=0.2, respectively) (data not shown). No significant difference between ≥VGPR compared <VGPR was observed in TTD (p=0.5) (data not shown). CONCLUSION: In this limited retrospective study, we showed that R-MIDD pts were diagnosed late in the disease when pts already developed severe CKD. R-MIDD pts frequently had a concomitant diagnosis of multiple myeloma. Despite treatment with novel agents and ASCT, only a third of pts had a renal response and a third of pts required eventual dialysis. This study highlights the need for early diagnosis of R-MIDD and better treatments for this disease. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

MO135: Efficacy and Safety of Bortezomib Combined with Autologous Stem Cell Transplantation in the Treatment of MGRS

Abstract BACKGROUND AND AIMS To evaluate the efficacy and safety of bortezomib combined with autologous stem cell transplantation (ASCT) in the treatment of monoclonal gammopathy of renal significance (MGRS). METHOD The clinicopathologic data of 16 patients with non-AL MGRS who received bortezomib combined with ASCT in Jinling Hospital of Nanjing University School of Medicine from February 2012 to June 2021 were retrospectively analysed. RESULTS Twelve patients were male and four were female, with a median age of 49 years, a median serum creatinine was 1.71 mg/ dL (1.45, 2.09) and a median eGFR wad 42.1 mL/min/1.73 m2 (29.0, 51.6). Renal pathological types included seven patients were light chain deposition disease, two patients were heavy chain deposition disease, one patient was light and heavy chain deposition disease, five patients were light chain proximal tubulopathy and one patient was proliferative glomerulonephritis with monoclonal immunoglobulin deposition. Sixteen patients received bortezomib-based induction therapy with a median three courses before transplantation. Stem cells were successfully collected from all patients and CD34 + cell counts were 4.4–13.55 × 106/kg (8.77 ± 3.29 × 106/kg). All patients had successful haematopoietic reconstitution, and a median time of achieving granulocyte count of 500/L was 10 (9, 10) days, and a median time of achieving platelet count of 20 000/L was 12 (11, 13) days. The major treatment complications during transplantation were mucositis (87.5%), diarrhoea (62.5%), fever (56.3%), and nausea and vomiting (18.8%); the other rare complications were acute kidney injury, skin rashes and liver function damage. Haematologic responses were achieved in 15 patients (93.8%), with 10 patients (62.5%) achieved complete responses, 3 patients (18.8%) achieved very good partial responses, 2 patients (12.5%) achieved partial responses, and 1 patient had no haematologic responses. Before treatment with ASCT, seven patients (43.8%) achieved partial response, of which four achieved complete response after ASCT, and one patient did not achieve hematologic response but achieved complete response after ASCT. A total of 12 patients (75%) achieved renal response before ASCT and 14 patients (87.5%) achieved renal response after ASCT. The median follow-up time was 43.5 months. One patient died during the follow-up due to infection, and one patient developed end-stage renal disease during the follow-up. Three patients relapsed, with a median time of 49 months. CONCLUSION Our data demonstrated that ASCT is a safe and effective treatment for rigorously selected non-AL MGRS patients, with few serious treatment complications and high haematological and organ response rates.

A Young Asian Man with Heavy Chain Deposition Disease

A Young Asian Man with Heavy Chain Deposition Disease

Heavy chain deposition disease presenting with raised anti-GBM antibody levels; a case report

BackgroundMonoclonal immunoglobulin deposition disease (MIDD) is a rare condition accounting for < 1% of histopathological diagnoses made on kidney biopsy1. The best outcomes are seen in those diagnosed and treated promptly, but delay to diagnosis is common with the largest series reporting a median time from onset of renal impairment to diagnosis of 12 months2. Here, we report a case of the heavy chain subset of MIDD presenting with positive anti-glomerular basement membrane (anti-GBM) antibodies obscuring the true diagnosis.Case presentationHere, we present a challenging case presenting with oedema, haematoproteiuria, and new renal impairment. Anti-GBM antibodies were positive and prompted treatment as atypical anti-GBM disease. However, they were ultimately proven to be monoclonal and secondary to myeloma. The final diagnosis facilitated effective myeloma treatment which led to complete remission and independence from renal replacement therapy.ConclusionsThis case reinforces the importance of comprehensive histopathological and haematological assessment in making the correct diagnosis. Here it facilitated effective treatment and recovery of renal function.

SAT-168 RAPIDLY PROGRESSIVE RENAL FAILURE IN A DIABETIC: AN INTERESTING CASE REPORT

The prevalence of non-diabetic nephropathy in patients with diabetes has been reported to vary widely between 12% to 79%. Various studies have reported Minimal change disease, Focal segmental glomerulosclerosis and IgA nephropathy as the commonest non-diabetic glomerular disease in patients with diabetes. Here we are reporting an interesting case of rapidly progressive glomerulonephritis in a patient with type 2 diabetes. Case report:A 55 year old male presented with Oliguria and Dyspnea since 1 week, with history of multiple pustules over body since 3 days. There was no history of cough, hemoptysis, fever, loin pain or dysuria. He had a past history of Hypertension and Diabetes since 15 yrs. He had history of NSAID intake since 1yr. On examination he was dyspneic, he had pallor, edema and pustules all over the body. His systemic examination was within normal limits. Blood Investigations:Urine routine-3+ proteinuria, 6-8 WBCs and no RBCs, Urine protein creatinine ratio- 6.5, Blood urea- 123mg/dL, and Serum creatinine- 8.4mg/dL. He was suspected to have RPRF and serum complements were sent. His C3 was 57(low) and C4 was 19 (normal), ANA and ANCA were negative. A provisional diagnosis of Infection related Glomerulo Nephritis(IRGN). However, in view of symptoms pre-dating appearance of skin lesions, renal biopsy was done. Light microscopy showed 8 glomeruli, of which one was globally sclerotic.4 glomeruli show cellular crescents. Endocapillary proliferation with hypercellularity and lobular accentuation was seen. Mesangial nodules which were weakly PAS and silver positive and blue on trichrome are seen in all the glomeruli. The nodules were almost of uniform size and distributed evenly within and between glomeruli. Tubular epithelial cell injury noted, Tubular basement membrane appeared prominent. Tubules showed 20% atrophy. Interstitium showed 30% fibrosis with lymphocyte infiltration. Blood vessel showed medial wall thickening. Congo red stain negative. Immunoflorescence showed IgG (+3) linear positivity over the tubular basement membranes, Bowmans capsule, and also positive over the mesangial nodules. Kappa and lambda light chains were negative. IgM, IgA, C3 and C1q were negative. Electron microscopy showed punctate deposits along the inner aspects of the Glomerular basement membrane, prominent mesangial nodular expansion and mild to moderate foot process effacement. Tubular Basement Membrane showed similar punctate deposits. He was hence diagnosed as having Gamma heavy chain deposition disease. He was treated with Bortezomib in view of logistic reasons. He had partial renal recovery with creatinine stabilised at 4 mg/dl and dialysis independent. Nodular lesions in Diabetes mellitus isn’t always diabetic nephropathy. HCDD( Heavy chain deposition disease) is a differential to consider in case of nodular glomerular lesions. Immunofluorescence is an important tool for diagnosis. In our case, preliminary investigations were suggestive of a IRGN, however biopsy gave the diagnosis. Hence, there must be low threshold for biopsy in doubtful cases. Also, HCDD presenting as rapidly progressive glomerulonephritis is extremely rare with very few cases reported. Treatment should be considered in view of nephrotoxicity of the Heavy chains, even in absence of a hematological disorder.

Heavy Chain Deposition Disease: Clinicopathologic Characteristics of a Chinese Case Series

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. Case series. 25 patients with biopsy-proven HCDD were studied retrospectively. 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. Retrospective study, single-center experience. 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.

MGCS : an IgG-lambda monoclonal gammopathy associated with renal failure, lung disease and cutis laxa

Renal diseases are frequently associated with monoclonal gammopathies. Heavy chain deposition disease (HCDD) is an extremely rare condition, one of the 3 entities of monoclonal immunoglobulin deposition disease (MIDD). It is characterized by the presence of nodular glomerulosclerosis and glomerular and tubular deposition of monoclonal HC without associated light chains (LC). Here, we reported a case of HCDD associated with other manifestations, e.a. pulmonary fibrosis and cutis laxa. A 38-year-old Polish woman was referred to the emergency room for a 2-month history of fatigue, 10 kg weight gain and NYHA II dyspnea.

Successful treatment of gamma 1 heavy chain deposition disease with bortezomib and dexamethasone

Heavy chain deposition disease (HCDD) is a rare complication of plasma cell dyscrasias, characterized by nonamyloid tissue deposits of incomplete monoclonal heavy chains in renal tissues. We report the case of a 78-year-old female with HCDD who was successfully treated with bortezomib and dexamethasone (BD); histopathological improvements were confirmed by kidney biopsy after 2 years of chemotherapy. She presented with renal insufficiency, proteinuria, hematuria, hypogammaglobulinemia, and hypocomplementemia. Renal biopsy showed diffuse global nodular glomerulopathy with the deposition of IgG1 and C3 in the glomeruli and on the tubular basement membrane. Kappa and lambda light chains were not detected. Staining for the constant regions of the gamma heavy chain revealed the absence of the CH1 domain. These findings are consistent with those of gamma 1 HCDD. Results of liquid chromatography-tandem mass spectrometric analysis were consistent with the immunohistochemical results. Two years after weekly BD therapy, normalization of the kappa/lambda ratio and reduction of urinary protein excretion were achieved. A follow-up biopsy showed remarkable diminution of nodular lesions of glomeruli and deposits of IgG and C3.

Heavy chain disease: a rare case report of adult nephrotic syndrome

Monoclonal immunoglobulin deposition disease is a systemic disorder characterized by the deposition of immunoglobulins as nonfibrillar material in various organs. Three subtypes have been reported: light chain deposition disease, light and heavy chain deposition disease and heavy chain deposition disease. Among these, light chain deposition disease is the most prevalent. Reports of light and heavy chain and heavy chain disease are rare, with fewer than two dozen documented cases in the world literature and very few from India. Heavy chain disease is characterized by glomerular, tubular, and vascular wall deposition of monoclonal heavy chains without associated light chains. We present the case of a 51-year man, who presented with a 3-month history of pedal edema, hypertension detected 3 months ago, and mild renal failure Estimated Glomerular filteration rate (eGFR) 66 ml/min/1.73 m2; histopathology showed heavy chain deposition disease. The case emphasizes the need for a thorough workup for plasma cell dyscrasias when we see membranoproliferative pattern in adult patients. This patient was treated with bortezomib-based regimen and after 3 months achieved near-complete remission of proteinuria with improvement in serum creatinine.

IgA kappa light and heavy chain deposition disease in multiple myeloma.

A 46-year-old patient was referred to our unit with acute renal failure, his serum creatinine having risen from 137 to 431 μmol/l in eight months. He was born in the Republic of the Congo and had lived in France since 2009. He had no significant previous medical history. On admission, clinical examination was normal except for high blood pressure. Blood analyses confirmed renal impairment. Urine analyses were significant for proteinuria (urinary protein to creatinine ratio 1 g/g), haematuria (105 red cells/ml) and leucocyturia (104 white cells/ml). Serum protein electrophoresis revealed an M-spike and urine protein electrophoresis showed light-chain proteinuria. The paraprotein was identified by immunofixation as immunoglobulin (Ig) A kappa. Bone marrow examination showed 28% clonal plasma cells. Kidney biopsy revealed Congo red-negative thickening of glomerular capillary walls and tubular basement membranes, with peritubular multinucleated giant cells (top left). Electron microscopy showed granular electron-dense material along the lamina rara interna of the glomerular capillary walls and along the outer aspect of the tubular basement membranes (top right). Immunofluorescence confirmed the diagnosis of light and heavy chain deposition disease (LHCDD) by demonstrating staining for IgA heavy chain (bottom left) and kappa light chain (bottom right), without staining for lambda light chain. Haemodialysis was initiated and the patient received first line chemotherapy with bortezomib, cyclophosphamide and dexamethasone. Eight months later, he exhibited an excellent partial haematological response. However, his renal function did not improve and he still required dialysis. Light and heavy chain deposition disease is a very uncommon subtype of monoclonal immunoglobulin deposition disease and only small numbers of cases of IgA kappa LHCDD have been reported. The authors thank the HUPNVS of Assistance Publique - Hôpitaux de Paris for funding publication fees.

Cutis laxa associated with monoclonal gammopathy: 14 new cases and review of the literature

Cutis laxa associated with monoclonal gammopathy: 14 new cases and review of the literature

Long-term renal survival of \u03b33-heavy chain deposition disease: a case report

BackgroundMonoclonal immunoglobulin deposition disease (MIDD) is characterized by the non-amyloid deposition of monoclonal immunoglobulin fragments in the basement membranes. Heavy chain deposition disease (HCDD) is a type of MIDD. HCDD is an extremely rare disease, and only three cases have been reported in Japan up to the present. The prognosis of HCDD is very poor, and optimal treatment has not been established. Only a few cases of HCDD with favorable long-term renal prognosis have been reported to date.Case presentationThe authors describe a 61-year-old woman who presented with massive proteinuria, progressive kidney impairment, and hypocomplementemia. Kidney biopsy was performed for a precise diagnosis. On light microscopy, glomerules were lobulated and presented with nodular sclerosing glomerulopathy with membranoproliferative glomerulonephritis-like features. Immunofluorescence studies were positive for IgG, C3, and C1q within the mesangial nodules and in a linear distribution along the capillary walls without associated deposition of light chains. Staining for IgG showed the presence of linear deposits along tubular basement membranes. The analysis of the IgG subclass stain demonstrated intense positivity for IgG3 only. Electron microscopy revealed non-organized electron-dense deposits in the expanded mesangial area and inner aspect of the glomerular basement membranes. In accordance with the histological findings, we diagnosed γ3-HCDD. There was no evidence of plasma cell dyscrasia as a result of bone marrow aspiration. Serum and urine monoclonal proteins were not detected by immunoelectrophoresis and immunofixation electrophoresis. The serum free light chain ratio was within normal range. At first, prednisolone was administrated at a dose of 40 mg/day. However, a therapeutic effect was not observed. Urinary protein was not decreased and renal function further deteriorated. Therefore, melphalan plus prednisolone (MP) therapy was initiated. After 4 courses of MP therapy, the clinical parameters, including proteinuria, serum creatinine, albumin, and complement level (C3 and C4) were ameliorated. To date, the patient has been followed for 28 months, and long-term renal survival has been observed.ConclusionsIn this case, hematologic disease such as multiple myeloma was not detected; however, MP therapy was effective. Recently, the novel concept of monoclonal gammopathy of renal significance (MGRS) has been reported. MIDD, which includes HCDD, is one category of MGRS. In MGRS, aggressive chemotherapy may induce favorable renal outcomes.