Randall-Type Monoclonal Immunoglobulin Deposition Disease: New Insights into the Pathogenesis, Diagnosis and Management

Abstract

Randall-type monoclonal immunoglobulin deposition disease (MIDD) is a rare disease that belongs to the spectrum of monoclonal gammopathy of renal significance (MGRS). Renal involvement is prominent in MIDD, but extra-renal manifestations can be present and may affect global prognosis. Recent data highlighted the central role of molecular characteristics of nephrotoxic monoclonal immunoglobulins in the pathophysiology of MIDD, and the importance of serum free light chain monitoring in the diagnosis and follow-up disease. Clone-targeted therapy is required to improve the overall and renal survival, and the achievement of a rapid and deep hematological response is the goal of therapy. This review will focus on the recent progress in the pathogenesis and management of this rare disease.

Monoclonal gammopathies of renal significance

“…In MIDD, up to 50% of patients may have at least one extra-renal manifestation (cardiac, liver, central nervous system) but they are often asymptomatic or less symptomatic compared to patients with AL amyloidosis. 6 Cryoglobulinemia is a systemic disease presenting with broad clinical features and severity, including arthralgia, purpura, skin ulcers, neuropathy and life-threatening complications, such as hyperviscosity syndrome in type I cryoglobulin. 7 The commonest indications for a renal biopsy in MGRS are proteinuria and renal impairment that are otherwise unexplained.…”

Long-term outcomes and renal responses following autologous hematopoietic stem cell transplantation for light chain deposition disease: a retrospective study on behalf of the Chronic Malignancies Working Party of the European Society for Blood and Marrow Transplantation

“…It is frequently associated with plasma cell disorders such as multiple myeloma (MM) or other B cell lymphoproliferative disorders though, sometimes no clonal B lymphocytes/plasma cells can be identified. LCDD typically involves organs, the kidneys being the cardinal organ involved, but also rarely the heart, liver and peripheral nerves [1][2][3][4][5][6][7] .…”

Randall-Type Monoclonal Immunoglobulin Deposition Disease in Bone Scintigraphy

“…Monoclonal immunoglobulin deposition disease (MIDD) is a rare complication of clonal B-cell disorder. 7,8 The disease is caused by linear deposits of monoclonal immunoglobulins, usually light chains (LCDD), and sometimes heavy chains (HCDD) or both (LHCDD), along basement membranes. MIDD can occur either in the context of multiple myeloma or monoclonal gammopathy of renal significance.…”

“…Hutt et al 5 and Wakfie-Corieh et al 6 highlighted that cardiac and extracardiac uptakes are not specific for ATTR amyloidosis and must be interpreted in the clinical and biological context to avoid pitfalls. Monoclonal immunoglobulin deposition disease (MIDD) is a rare complication of clonal B-cell disorder 7,8 . The disease is caused by linear deposits of monoclonal immunoglobulins, usually light chains (LCDD), and sometimes heavy chains (HCDD) or both (LHCDD), along basement membranes.…”

“…The cardiac biopsy revealed unorganized deposits of κ light chains along the cardiac fibers ( C ), not colored by Congo red ( B ), without λ light chains deposits ( D ). Finally, the patient was treated with daratumumab-bortezomib-cyclophosphamide-dexamethasone 8,10 . MIDD appears to be an important pitfall and a differential diagnosis of ATTR amyloidosis in bone scintigraphy.…”