Current pathophysiological classification of the main MGCS-related disorders: MGCS due to deposition of all or part of the MIg
| . | Ultrastructural appearance of deposits . | Main characteristics of monoclonal gammopathy . | Main organ(s) involved . | Reference . |
|---|---|---|---|---|
| Organized | ||||
| AL amyloidosis | Fibrillar | λ LC (75%), κ LC (25%), IgM <10% | Systemic (heart 80%, kidney 70%) | 8,57 |
| Type I cryoglobulinemia | Microtubular/crystalline | IgG or IgM | Systemic (skin +++, kidney, peripheral nerve, systemic symptoms [crystal cryoglobulin]) | 12,28 |
| Immunotactoid glomerulopathy/GOMMID | Microtubular | CLL-like clonal proliferation (50%) | Kidney | 13 |
| Acquired Fanconi syndrome | Crystalline | κ LC (>90%, mostly Vk1) | Kidney (proximal tubulopathy) | 9 |
| Crystal storing histiocytosis | Crystalline | κ LC | Systemic (kidney, cornea, joints, lymphoid tissue) | 10 |
| Crystalline keratopathy | Crystalline | IgG | Cornea | 11 |
| Nonorganized | ||||
| MIDD | LCDD: LC only (usually κ LC) (80%, Vk1 and Vk4) HCDD: truncated HC only (mostly γ1 and γ3) LHCDD: LC + truncated HC | Systemic (kidney [∼100%, glomerular and tubular basement membrane], liver [30%], heart [30%]) | 14,51,61 | |
| PGNMID | Usually IgG3 | Kidney | 15 | |
| Macroglobulinosis | IgM | Skin (dermis) | 16 |
| . | Ultrastructural appearance of deposits . | Main characteristics of monoclonal gammopathy . | Main organ(s) involved . | Reference . |
|---|---|---|---|---|
| Organized | ||||
| AL amyloidosis | Fibrillar | λ LC (75%), κ LC (25%), IgM <10% | Systemic (heart 80%, kidney 70%) | 8,57 |
| Type I cryoglobulinemia | Microtubular/crystalline | IgG or IgM | Systemic (skin +++, kidney, peripheral nerve, systemic symptoms [crystal cryoglobulin]) | 12,28 |
| Immunotactoid glomerulopathy/GOMMID | Microtubular | CLL-like clonal proliferation (50%) | Kidney | 13 |
| Acquired Fanconi syndrome | Crystalline | κ LC (>90%, mostly Vk1) | Kidney (proximal tubulopathy) | 9 |
| Crystal storing histiocytosis | Crystalline | κ LC | Systemic (kidney, cornea, joints, lymphoid tissue) | 10 |
| Crystalline keratopathy | Crystalline | IgG | Cornea | 11 |
| Nonorganized | ||||
| MIDD | LCDD: LC only (usually κ LC) (80%, Vk1 and Vk4) HCDD: truncated HC only (mostly γ1 and γ3) LHCDD: LC + truncated HC | Systemic (kidney [∼100%, glomerular and tubular basement membrane], liver [30%], heart [30%]) | 14,51,61 | |
| PGNMID | Usually IgG3 | Kidney | 15 | |
| Macroglobulinosis | IgM | Skin (dermis) | 16 |
AL amyloidosis is the most frequent type, with an incidence of ∼10 per million inhabitants per year in Western countries. MIDD incidence is estimated to be 10-fold lower. Other types of MGCS due to deposition of MIg are rare (type I cryoglobulinemia and PGNMID), even scarcer (Fanconi syndrome), or exceptional (macroglobulinosis and crystalline keratopathy).
CLL, chronic lymphocytic leukemia, GOMMID, glomerulonephritis with organized microtubular monoclonal immunoglobulin deposits; HCDD, heavy-chain deposition disease; LCDD, light-chain deposition disease; LHCDD, light- and heavy-chain deposition disease.