Monoclonal Gammopathies

In this situation, a monoclonal protein is present in serum ("M" protein). This is an immunoglobulin which persists constantly at an elevated level over many years without the development of any malignant systemic disease. It is caused by the proliferation of a single clone of mature differentiated B lymphocytes producing this y-globulin.

This monoclonal immunoglobulin may not only be directed against proteins of the coagulation pathway (usually factor VIII) but may also be an antibody against the phospholipid of tissue thromboplastin, resulting in a 'lupus-like' anticoagulant/Antiphospholipid Syndrome. The first such case was described by Thiagarajan [91] in 1980. This was an IgM which reacted specifically with phos-phatidylserine and phosphatidylinositol and prolonged the PTT and RVVT in vitro.

"Lupus anticoagulants" are generally polyclonal immunoglobulins.

Reviewing patients over a 20-year period at the Mayo Clinic who had demonstrated a serum IgM monoclonal gammopathy, it was found that patients could be classified into several groups, the majority (56%) falling into "monoclonal gammopathy of undetermined significance" (MGUS) with no constitutional symptoms, hepatosplenomegaly, lymphadenopathy or anaemia who required no chemotherapy [92,93]. This is also referred to as benign monoclonal gammopathy.

These paraproteins are also produced with other B-cell disorders which include multiple myeloma, and Waldenstrom's macroglobulinaemia mainly. To a lesser extent they may also be produced in patients with lymphoma, chronic lymphocytic leukaemia and hairy cell leukaemia. Usually haemolytic complications ensue but these complications are often multifactorial and not due to the paraproteinemia alone (e.g., thrombocytopenia, renal failure, clotting factor depletion, etc.). Splenectomy often improves platelet damage by this organ.

In patients with MGUS, myeloma or Waldenstrom's macroglobulinaemia, the monoclonal protein may demonstrate unusual specificities e.g., antistreptolysin, antinuclear, dsDNA, apolipoprotein or even anticardiolipin activity [94], Up to 10% of MGUS sera demonstrate autoantibody activity without autoimmune disease. aPL in patients with MGUS were studied by Stern et al. [95] in 1994. In MGUS sera it was found that they manifested a significantly higher (p < 0.01) incidence of aPL than did normal controls.

Monoclonal gammopathies with LA activity and/or a biological false positive test for syphilis (BFP STS) have been described by many investigators [96-98].

However clinical manifestations of the APS have not been frequent. A 73-year-old male documented by Drusin et al. [99] with Waldenstrom's macroglobulinaemia and a BFP-STS experienced multiple myocardial infarctions.

Lechner and Pabinger-Fasching [100] also refer to one of their 5 patients with paraproteinemia who developed thrombotic complications.

Bellotti et al. [101] in their study of three patients with monoclonal gammopathies and "lupus-like" anticoagulants included one each with MGUS, myeloma and lymphoma. Only the patient with lymphoma had any APS related complaints, viz., recurrent TIA.

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Responses

  • baillie
    Is monoclonal gammopathy an autoimmune disease?
    5 years ago

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