Polyclonal Hypergammaglobulinemia Causes

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M protein

M protein albumin alpha-2

aHphia-l beta gamma

Figure 1 Serum protein electrophoresis. On the left is a normal pattern. Note the gamma globulin band is wide and the densito-metric tracing is broad-based. On the right is a monoclonal gammopathy pattern. The gamma region contains a narrow band and the densitometric tracing shows a tall narrow spike'

cause of the IgE increase is not known. Hyper-IgD syndrome has also been described. These patients may present with constitutional symptoms including fever and headaches, and they may have lymphaden-opathy. Still another group of patients may have hyper-IgG syndrome. This is a familial disorder. There is no underlying infectious or inflammatory condition, and there is no evidence of an autoimmune disease or lymphatic neoplasm. The class restriction has been linked to class-specific regulatory T cell clones.

Underlying diseases causing polyclonal gammopathy

The most profound polyclonal hypergammaglobulinemia is found in chronic liver disease, rheumatoid arthritis and Sjögrens syndrome. The gamma globulin increase in Sjögrens syndrome is characteristically associated with very high levels of rheumatoid factor (IgM anti-IgG immunoglobulin). Uncommonly, serum hyperviscosity occurs, producing signs and symptoms of impairment of blood clotting and blood flow.

Known infectious causes of polyclonal hypergammaglobulinemia include parasitic infections such as malaria, schistosomiasis, strongyloidiasis and leishmaniasis, and fungal infections such as paracocci-diodomycosis and histoplasmosis (Table 1). Other causes include bacterial infections such as brucellosis, spirochete infections such as borrelia (Lyme disease), and rickettsial infections. Various viral infections may also cause polyclonal hypergammaglobulinemia. These include hepatitis, vaccinia, and varicella zoster infections.

Autoimmune disorders commonly manifest polyclonal hypergammaglobulinemia. Among these, rheumatoid arthritis and Sjögrens syndrome cause the most profound polyclonal increase in gamma globulin. In systemic lupus erythematosus, the increase in polyclonal immunoglobulin is usually modest but many different autoantibodies may be present, such as antinuclear antibody, rheumatoid factor, cardiolipin antibodies and antibodies against red blood cells, neutrophils and platelets. The deregulated expression of 1L-6 has been implicated in the polyclonal B cell activation and hypergammaglobulinemia seen in autoimmune diseases. Continuous 1L-6 stimulation in mice produces hypergammaglobulinemia and mimics the chronic B cell hyperplasia of Castleman's disease, or giant lymph node hyperplasia. Increase in serum ßi-microglobu-lin (the light chain of the class I major histocompatibility complex) accompanies the polyclonal hypergammaglobulinemia seen in lupus and other autoimmune disorders such as Sjogren's syndrome. A monoclonal gammopathy or B cell lymphoma may develop in patients with Castleman's disease or Sjögrens syndrome.

In common with other neoplasms, some malignant lymphomas and lymphoproliferativc disorders may be associated with polyclonal hypergammaglobulinemia. Among these are non-Hodgkins and Hodgkins lymphoma and acute lymphocytic and myelogenous leukemia. While polyclonal hypergammaglobulinemia is uncommon in these conditions, it occurs in up to one-half the cases of peripheral T cell leukemia/lymphoma and chronic myelomonocvtic leukemia. Polyclonal hypergammaglobulinemia is common in patients with angioimmunoblastic lym-phadenopathy with dysproteinemia (AILD). The polyclonal hypergammaglobulinemia and other disease manifestations may disappear when a causative

Table 1 Causes of polyclonal gammopathy

Infectious and inflammatory Autoimmune



Chronic liver disease Parasitic Infections Malaria

Schistosomiasis Strongyloidiasis Leishmaniasis Fungal infection Paracoccidiodomycosis Histoplasmosis Bacterial infection Brucellosis Tuberculosis Spirochetes

Lyme disease Viral infections Hepatitis Varicella zoster Vaccinia Rickettsial disease

Rheumatoid arthritis Sjögrens syndrome Systemic lupus erythematosis Polymyositis Mixed connective tissue disease

Metastatic carcinoma Malignant lymphoma Hodgkins disease Acute lymphocytic leukemia Acute myelogenous leukemia Peripheral T cell leukemia/lymphoma Chronic myelomonocytic leukemia

Angioimmunoblastic lymphadenopathy with dysproteinemia (AILD) Natural killer cell/large granular lymphocyte syndrome Castlemans disease Acquired immunodeficiency syndrome (AIDS) Benign hypergammaglobulinemic purpura of Waldenstrom medication is discontinued. In most patients with AILD however, a latent T cell lymphoma is present. Patients with natural killer (NK) cell/large granular lymphocyte (LGL) syndrome have a polyclonal hypergammaglobulinemia. Another idiopathic acquired and uncommon polyclonal hypergammaglobulinemia is benign hypergammaglobulinemia purpura of Waldenstrom (BHPW). Patients have characteristic vascular purpura of the lower extremities. Malignant transformation in BHPW is uncommon.

Polyclonal hypergammaglobulinemia is frequently seen in disorders characterized by immune deficits. One example is the acquired immune deficiency syndrome (AIDS). In AIDS, there is a decreased CD4/CD8 T cell ratio, yet the level of polyclonal Ig is paradoxically increased. B and T lymphocytes have a decreased response to mitogen. Some AIDS patients develop monoclonal gammopathy and eventually a neoplastic process of B cells such as lymphoma or multiple myeloma.

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  • christopher
    Why tgere is hypergammaglobinemia in sle?
    2 years ago
  • Odetta
    Is it common to have polyclonal gammopathy in alcohol related liver disease?
    2 years ago
  • narciso
    What is polyclonal hypergammaglobulinemia?
    1 year ago
  • nina
    Is a polyconal increase in grobulin region serious?
    1 year ago
  • berylla hayward
    Do you treat Polyclonal hypergammaglobulinemia with prednisone?
    1 year ago
  • aapo
    What is a ployconal increase in grobulin region?
    1 year ago
    What does hypergammaglobulinemia suggestive of chronic inflammatory response mean?
    1 year ago
  • Regina
    Can autoimmune disease cause polyclonal hypergammoglobulinemia?
    1 year ago
  • prudenzia
    What causes elevations of igm due to polyclonal immunoglobulin production?
    1 year ago
  • Nasih
    Is it safe to go in crowd with polychonal hypergammaglobulimia?
    11 months ago
  • Nunzia
    Can seronegative arthritis cause hypergammaglobulinemia?
    11 months ago
  • rené
    What is hypergammaglobulinemia in sjogren's syndrome?
    10 months ago
  • medhanit
    What AI diseases cause polyclonal hypergammaglobulinemia?
    9 months ago
  • geremia
    What does increase in polyclonal gamma globulins?
    9 months ago
  • jessika kohler
    What does Polyclonal gammaglobulinemia with Positive ANA?
    9 months ago
  • maura
    What does polyclonal hypergammaglobulinemia mia with no evidence of monoclonal gammopathy means?
    7 months ago
  • René Rothschild
    What does polyclonal gammopathy with increased beta globulins and decreased albumin?
    7 months ago
    Is a polyclonal increase in gammaglobulins anything to worry about?
    7 months ago
  • Bruto
    Can ms cause a polyclonal pattern on a spe?
    6 months ago
  • arthur
    How to find what causes polyclonal gammopathy?
    6 months ago
    How do you treat polyclonal IgG gammopathy?
    4 months ago
  • milen
    What does it mean if the protein electrophopresis has a polyclonal background?
    3 months ago
  • aira
    Can vasculitis cause polyclonal gammopathy?
    3 months ago
  • wegahta adonay
    How high is globulin in rheumatoid arthritis?
    2 months ago
  • Murdo Duncan
    What doea polyclonal increase in beta / gamma region?
    2 months ago
  • samira
    Does globulin rise in response to infection?
    1 month ago
  • Kedija
    What are polyclonal hypergamminuliemia?
    1 month ago
  • Roman
    What kind of specialist manages polyclonal hypergamma globulinemia?
    13 days ago
  • paul
    What is hypergammaglobulinemia and rheumatoid arthritis?
    5 days ago

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