Paraproteinemia

Elevated concentrations of monoclonal immunoglobulins or fragments thereof in serum. These immunoglobulins are called paraproteins, or the so-called M-component (M-monoclonal). Protein monoclonality is caused by excessive proliferation of a single clone of plasma cells, often on the basis of malignant proliferation - plasmacytoma. Depending on the cell type, complete immunoglobulins of the IgG or IgM class, or only light or heavy chains, are synthesized.

The presence of paraproteins causes a narrow and high peak in the γ-globulin region during serum protein electrophoresis.

If only immunoglobulin light chains are synthesized, they penetrate the glomerular membrane into the urine, where they can be detected as a so-called Bence-Jones protein. This protein is not detectable by conventional test strips - urine electrophoresis or heating (protein denaturation) is required for capture. Bence-Jones protein can cause kidney damage. Cylinders may form in the distal tubules and cause nephropathy, or crystal formation in the cytoplasm of proximal tubule cells may cause Fanconi's syndrome.

The concentration of paraprotein in the blood reflects the extent and activity of the pathological clone of the cells. At high concentrations, it causes the so-called hyperviscosity syndrome (visual impairment, thrombosis, neurological symptoms). If the M-component has the character of cryoglobulins, specific microcirculatory disorders, Raynaud's syndrome (cryoglobulins precipitate in the cold acral parts of the body). Paraprotein production is also accompanied by a decrease in the production of normal Ig and their increased degradation. Typically, resistance to infections is reduced.

Paraprotein production is characteristic of the following lymphoproliferative syndromes : multiple myeloma, Waldenström's macroglobulinemia , primary amyloidosis , heavy chain disease and MGUS (monoclonal gammopathy of uncertain severity).

Multiple myeloma (myeloma)
Progressive skeletal damage by neoplastic proliferation of plasma cells, diffusion form. Increased IgG or IgA production. Possible capture of Bence-Jones protein in the production of light chains in urine. The liver, spleen and nodules are not enlarged. Bone tissue increasingly resorbed by osteoclasts, rapid development of osteoporosis , destructive and osteolytic changes of axial parts of the skeleton, pathological fractures. Hypercalcaemia due to paracrine production of osteolytic factors by malignant cells. Impaired renal tubular function ( glycosuria, aminoaciduria,…), secondary normocytic and normochromic anemia.

Waldenstrom's macroglobulinemia
Neoplastic proliferation of IgM- producing plasma cells. Hepatomegaly, splenomegaly, lymphadenopathy are present. Bone metabolism is not disturbed, there is usually no proteinuria. Cryoglobulin, Raynaud's syndrome, anemia, hemorrhagic diathesis present.

Primary Amyloidosis
It is actually caused by multiple myeloma. Amyloid fibrils contain parts of Ig light chains or whole light chains or parts of heavy chains. The source is a pathological plasma cell clone. Non-specific symptoms (fatigue, weight loss, syncope …).

Heavy chain disease
Pathological production of parts of heavy Ig chains that are present in plasma and urine. There are three forms of the disease (according to the types of heavy chains): γ, α, μ. It may be accompanied by lymphoma or other lymphoproliferative diseases.

MGUS - monoclonal gammopathy of uncertain severity
Expansion of a single plasma cell clone that does not behave as malignant for unknown reasons. It most often involves the production of IgG and IgA. Quite common, requires monitoring.

Related articles

 * Dysproteinemia
 * Plasma proteins
 * Hypergamaglobulinemie

Category: Pathophysiology, Pathobiochemistry, Hematology, Nephrology, Internal medicine