Immunoglobulin M (IgM)

Sample for Immunoglobulin M (IgM)

1. Fresh serum of the patient is needed.
2. Analyze the sample as soon as possible or can store it at 4 °C for a few hours (less than 72 hours).
3. The sample is stable at -20 °C for 6 months.

Indications for Immunoglobulin M (IgM)

1. Used to detect monoclonal gammopathy.
2. It diagnoses Waldenstrom macroglobulinemia.
3. It is advised for immune deficiencies.
4. It is advised in acquired IgM immunodeficiencies.
5. Earliest immunoglobulin (IgM) in the diagnosis of infectious diseases.

Immunoglobulin M (IgM) facts:

1. IgM exists in two forms: 
   1. Monomeric IgM form exists as a B- cell receptor for antigen.

2. Pentameric IgM form is present in the blood. It consists of five basic units and is joined by the J-chain.

3. It is 10% of the total immunoglobulin with a molecular weight of 900,000 and is 19 S.
   1. Its concentration is 120 mg/dl.
   2. Its molecular weight is 900,000 and 19S.
4. There are 10 potential sites for antigen binding.
5. IgM is the first antibody production in response to antigenic stimulation, called Primary immune response.
   1. In primary response, there is the stimulation of B-Lymphocytes which form the plasma cells and produce IgM.
6. IgM, as a pentamer form, is the most effective stimulator of the complement system for a lytic reaction.
7. In fetal life, this is the first immunoglobulin that appears first, and its raised level in neonates indicates intrauterine infection.
8. IgM has a half-life of 10 days.
9. It is predominantly present in the intravascular spaces.
10. It is a poor toxin-neutralizing antibody.
11. It can not cross the placental barrier.
12. Cold agglutinins are IgM antibodies.
    1. These are usually directed against the antigen on the RBC membrane.
    2. These may be 15% to 30% of the Coomb’s positive antibodies.

Waldenstrom’s macroglobulinemia:

Definition of Waldenstrom’s macroglobulinemia:

1. Waldenstrom’s macroglobulinemia is a hyperviscosity syndrome caused by low-grade small-cell lymphoma and produces abundant monoclonal IgM immunoglobulin.
2. These are lymphoproliferative disorders characterized by monoclonal IgM production.
3. This IgM molecular weight is 1,000,000 daltons or 19S.

 S/S of Waldenstorm’s macroglobulinemia:

1. This condition has typical clinical S/S:
   1. There is hyperglobulinemia with rouleaux formation.
   2. There is hyperviscosity syndrome. This may lead to the following:
      1. Neurological abnormalities.
      2. Shortness of breath.
      3. There are visual abnormalities and changes in the retina.
      4. In some patients, it is interpreted as malignant lymphoma.
   3. Lymphadenopathy.
   4. Hepatosplenomegaly.

Diagnosis of Waldenstrom’s macroglobulinemia:

1. 10% to 30% of the patients secrete Bence Jones proteins in the urine.
2. IgM protein is >3 g/dL.

3. Total proteins and globulins are markedly increased.
4. There is severe anemia. It is usually normochromic and normocytic.
5. There is prominent rouleaux fiormation.
6. Differential count:
   1. White cells show leucopenia with lymphocytosis. But there is no evidence of leukemia.
   2. There is an increased number of eosinophils and monocytes.
7. There is a positive Coomb reaction, so the difficulty in blood cross-matching.
8. ESR is markedly raised.
9. Lymph node biopsy shows a mixture of mature lymphocytes and plasmacytoid lymphocytes.
   1. In some cases, the picture is a diffuse type of lymphocytic lymphoma.
10. Bone marrow aspirate shows:
    1. Normal changes or hypercellular marrow.
    2. In some cases, this aspirate may be hypocellular.
    3. Nonspecific lymphoid infiltrates, and there are atypical lymphocytes.
    4. Lymphoma-like infiltrate.
11. Radiological studies do not show punched-out osteolytic areas like myeloma.

Normal Level of Immunoglobulin M (IgM)

Source 1

• To convert into SI unit x 10 = mg/L

Source 2

• Adult = 55 to 375 mg/dL
• Children = 20 to 200 mg/dL

Another source

1. 0 to <5 months = 26 to 122 mg/d
2. 15 to <24 months = 46 to 152 mg/dL
3. 2 to <4 years = 37 to 184 mg/d
4. 10 to <13 years = 41 to 255 mg/dL
5. 16 to <18 years =  49 to 201 mg/dL
6. More than 18 years = 37 to 286 mg/dL
   1. Values vary from different methodologies.

Decreased level of Immunoglobulin M (IgM) seen in:

1. Decreased levels are seen in congenital deficiency diseases.
2. In protein-losing syndrome.
3. Non-IgM myeloma.
4. Infancy and early childhood.

Increased level of Immunoglobulin M (IgM) is seen in :

1. Elevations of IgM may be due to polyclonal immunoglobulin production, which was seen in various infections.
2. An isolated increase in IgM level may be seen in viral infections, e.g., Viral hepatitis, infectious mononucleosis, and early response to bacterial or parasitic infection.
3. Increased levels of IgM may be seen in Rheumatoid arthritis, biliary cirrhosis, and some other chronic disorders.
4. Raised levels are also seen in Hyper IgM dysgammaglobulinemia, active sarcoidosis, collagen vascular diseases, and nephrotic syndrome.
5. Monoclonal  raised levels are seen in :
   1. Waldenstrom’s globulinemia.
   2. Lymphomas.
6. Chronic infections.
7. Liver diseases.