IgM globulins

The evidence for the role of intravascular IgM globulin has been reviewed (Section 2.3), and it seems that the chief function of IgM globulin is to protect the bloodstream. 

In all forms of glomerular nephritis in tropical populations in Africa, there was increased protein in the urine. In the selective proteinuria of the nephrotic syndrome most of the protein was mainly albumin and transferrin, with lower concentrations of IgG and other globulins. On the other hand, the urine of the nonselective proteinuria of the nephrotic syndrome is characterized by much higher concentrations of IgG, IgA, a2-macroglobulins, and some IgM. Differential protein clearance to establish selectivity of proteinuria has been discussed above. 

It consists primarily of IgG and contains trace amounts of IgA and IgM. y-Globulin provides the patient with passive immunity and does not require time for the development of an antibody response. It is believed to inhibit viral penetration of host cells, opsonize viral particles, activate complement, and stimulate cell-mediated immunity. 

When injected, azathioprine (Imuran) is rapidly converted to 6-mercaptopurine. The half-life of azathioprine after intravenous injection is 10 to 20 min, and that of 6-mercaptopurine is somewhat longer. The cytotoxic activity of these thiopurines is due to the conversion of mercaptopurine to 6-thiouric acid, a noncarcinostatic metabolite. This action is thought to block the excess synthesis of inosinic acid from its precursors, glutamine and phosphoribosylpyrophosphate. In addition, unlike cyclophosphamide, azathioprine is a potent anti-inflammatory substance that can cause a reduction in the number of monocytes and neutrophils at inflammatory sites. Antibody responses are also inhibited by azathioprine. Studies in humans have shown that azathioprine decreases the y-globulin and antibody levels, thus influencing IgG rather than IgM production. This makes azathioprine an effective immunosuppressant in the early phases of immune responses. It is less effective or completely ineffective in altering either the effector phase or already established reactivities. 

Globulins with quantification of Gamma globulin fraction (IgG, IgM, IgA, IgE)... 

Fig. 7.—Agar-diffusion patterns of anti-glucose antibodies with various glycoconjugates (A and B) and immunoglobulin antibodies (C and D) M = mixture of the two antibodies, a = antibodies specific for a-Glc-BSA, ft = antibodies specific for /3-Glc-BSA, 1 = a-GIc-BSA, 2 = /3-Glc-BSA, 3 = a-GIc-horse globulin, 4 = /3-Glc horse globulin, A = goat antirabbit IgA antibodies, G = goat anti-rabbit IgG antibodies, and M = goat anti-rabbit IgM antibodies. [Reprinted with permission from J. H. Pazur, F. J. Miskiel, N. T. Marchetti, and H. R. Shiels, Pharm. Pharmacol. Lett., 2 (1993) 232-235.]...

Figure 33.6. Classes of Immuno-Globulin. Each of five classes of immuno-globulin has the same light chain (shown in yellow) combined with a different heavy chain (y, a, p, 8, or e). Disulfide bonds are indicated by green lines. The IgA dimer and the IgM pentamer have a small polypeptide chain in addition to the light and heavy chains.

In decreasing concentrations, serum immunoglobulins consist predominantly of IgG, IgA and IgM with their subclasses Gi 4, Ai 2 and Mi 2- Quantitative changes of immunoglobuhns are only partially detected using electrophoresis the y-globulin fraction consists predominantly of IgG, while IgA and IgM are detectable in the p- or p/y-fraction. Catabolization of IgG depends on the respective immunoglobulin concentration, while IgM and IgA are catabolized independently of the sermn level. The half-hfe of IgG is 9—23 days, of IgA 6 days and of IgM 5 days. 

Chronic active hepatitis is associated with a strong elevation of IgG with normal or slightly elevated IgM and IgA. Marked elevations of IgG and IgA — with a strong parallel rise in the blood sedimentation rate (BSR), in y-globulin values and in total protein — are... 

The disease runs a course similar to that of an insidious infection with remittent fever (often with a dromedary curve during the day), tickling of the throat, diarrhoea and lymphadenopathy. Hepatosplenomegaly develops as a result of affected sinus endothelia and the subsequent neoformation and multiplication of these cells (a process which is also found in the lymph nodes). A blackish hyperpigmentation (face, hands, feet and abdomen) is a characteristic symptom of visceral leishmaniasis. Laboratory tests reveal a marked increase in IgM and y-globulins as well as anaemia, leucopenia, throm-... 

---