Antibody deficiency

In passive immunotherapy immune globulin (Ig) is an effective replacement in most forms of antibody deficiency (14). In the past, plasma was used instead of immune globulin, but plasma is rarely indicated in the 1990s because of the risk of disease, particularly AIDS, transmission. Because plasma contains many factors in addition to immunoglobulins (Igs), plasma is, however, of particular value in patients with protein-losing enteropathy, complement deficiencies, and refractory diarrhea. 

Primary immunodeficiency states, including both antibody deficiencies and combined deficiencies / Idiopathic thrombocytopenic purpura... 

Intravenous Immune Globulin (IGIV) IGIV is a product derived from blood plasma from a donor pool similar to the immune globulin (IG) pool, but prepared so it is suitable for intravenous use. IGIV does not transmit infectious diseases. It is primarily used for replacement therapy in primary antibody-deficiency disorders, for the treatment of Kawasaki disease, immune thrombocytopenic purpura, hypogammaglobulinemia in chronic lymphocytic leukemia, and in some cases of HIV infection. 

The commonest causes of death in the Jamaican patients with multiple myelomatosis were bronchopneumonia and other infectious complications, a finding which is compatible with the secondary antibody deficiency syndrome and impaired cellular immunity which occurs in patients with this disease. Bleeding manifestations and renal failure were not uncommon findings, and myeloma kidney was observed in 66% of the cases. Skeletal involvement was observed, but in many cases the typical lesions had to be searched for. Amyloidosis was present in as many as 21% of the patients (Tl) and this may be associated with the high number of patients in Jamaica that are known to excrete Bence Jones protein in myeloma (Mil). 

As mentioned previously, serial estimations of the immunoglobulin levels in patients with malignancies are useful indices in the assessment of response to treatment and of the course of the disease. They are therefore recommended. It is more than likely that the subnormal transformation of peripheral blood lymphocytes to plant mitogens which indicate impaired cellular immune responses coupled with the antibody deficiencies are responsible for the infection which frequently occurs in these patients. 

Important factors in the immunocompromised host predisposing to infection are granulocytopenia, T- or B-cell dysfunction, antibody deficiency. 

Three basic approaches are used to control viral diseases vaccination, antiviral chemotherapy, and stimulation of host resistance mechanisms. Vaccination has been used successfully to prevent measles, rubella, mumps, poliomyelitis, yellow fever, smallpox, chickenpox, and hepatitis B. Unfortunately, the usefulness of vaccines appears to be limited when many stereotypes are involved (e.g., rhinoviruses, HIV). Furthermore, vaccines have little or no use once the infection has been established because they cannot prevent the spread of active infections within the host. Passive immunization with human immune globulin, equine antiserum, or antiserum from vaccinated humans can be used to assist the body s own defense mechanisms. Intramuscular preparations of immune globulin may be used to prevent infection following viral exposure and as replacement therapy in individuals with antibody deficiencies. Peak plasma concentrations of intramuscular immune globulins occur in about 2 days. In contrast, intravenously administered immune globulin provides immediate passive immunity. 

Primary immunodeficiency Immune globulin (IV)2 Consult the manufacturer s dosing recommendations for the specific Primary immunodeficiency disorders include specific antibody deficiencies... 

Reid RR, Prodeus AP, Khan W, Hsu T, Rosen FS, Carroll MC, Endotoxin shock in antibody-deficient mice unraveling the role of natural antibody and complement in the clearance of lipopolysaccharide, J. Immunol., 159 970-975, 1997. 

IGIV is used either for antibody replacement or immuno-modulation. Some of the indications as replacement therapy include general or specific immunodeficiency states e.g., hepatitis A prophylaxis, chronic lymphocytic leukemia with hypogammaglobulinemia, multiple myeloma with specific antibody deficiency, low birth weight babies at risk for infection and infants/children with HIV. It is also used as an immune modulator in conditions such as idiopathic thrombocytopenic purpura and acquired hemophilia (Krensky et al., 2005 Shah, 2005). 

Bjorkander J. Antibody Deficiency Syndromes. Thesis. Sweden University of Gdteborg, 1985. 

The antibody deficiency associated with certain conditions is believed to result somehow from those conditions, to which it is therefore called secondary. Secondary AG and DG are 10-100 times commoner than the primary forms, which mostly occur on a genetic basis and are considered below (Section 5). 

Strictly speaking, the term dysgammaglobulinemia can be used only when antibody deficiency has been established hy challenging the patient with a series of antigens with known reliable normal ranges of responses (H32). In practice most cases of DG are associated with severe deficiency of IgM and/or IgA, and for convenience secondary DG here will indicate... 

In the majority of patients there is a clear picture of lymphoid neoplasia preceding the secondary antibody deficiency. In about half the patients with IgG-myelomatosis (about 20% of all those with malignant immunocytomata), it is clear that the high serum level of IgG paraprotein increases the catabolism, and lowers the serum level, of the normal IgG (S18). However, in the other 80% of malignant paraproteinemia, and in the other lymphoid neoplasias, it has been established that decreased IgG synthesis is responsible (A4), and it has already been noted (3.2, 3.3) that subnormal IgM and IgA are nearly always due to impaired synthesis. 

In a minority of patients there is a clear picture of long-standing antibody deficiency preceding the development of lymphoid neoplasia. It seems that the humoral defect results in overstimulation of the cellular mechanisms of immunity to a degree increasing the risk of mutation. Evidence that immunoglobulin deficiency can itself sometimes be primary to lymphoid neoplasia has been reviewed elsewhere (F12). 

Giedion and Scheidegger (G5) were the first to show that an electro-phoretically normal y-globulin could be associated with antibody deficiency. In their patient the serum immunoglobulin pattern showed a persistent absence of IgA and IgM with an apparently normal IgG. 

Over 20 patients (children and adults) are now recorded with a male to female ratio of 4 1. For most acquired antibody deficiencies, the rule is a fall in IgM, then in IgA, and finally in IgG. This is the pattern to be expected in adults (B5, G6), and a slow acquisition in childhood has also been observed (B27). In many such cases it may simply represent an incomplete expression of hypogammaglobulinemia of the sex-linked or non sex-linked varieties. It has also been recorded (G25) in a patient with 13-15 trisomy syndrome due to translocation. Patients with this serum immunoglobulin pattern seem to fall into two main groups, probably depending on the quality of the IgG-globulin. 

IgA deficiency has also been observed in 7 patients with central nervous system (CNS) disorders and in 5/7 patients with partial deletions of chromosome 18 (S26). The association with ataxia telangiectasia is not complete and probably represents a coincidence of genes, exemplified by the presence of either defect alone in relatives of propositi. It is of interest that other CNS defects are recorded with IgA deficiency, and partial deletions of chromosome 18 are also associated with mental retardation. It seems, however, that the predisposition to infection is closely correlated to IgA deficiency, so that ataxia telangiectasia per se does not justify separate classification as an antibody deficiency syndrome (SIO). 

Hobbs and Citron showed that normal serum immunoglobulin levels in a man 38 years old could be associated with a severe antibody deficiency syndrome corrected by y-globulin treatment (H19). Previous workers had shown that deficiencies of antibodies to measles virus (M19), to vaccinia virus (K3), and to other viruses (LIO) in the presence of apparently normal y-globulin, could result in overwhelming infections. However, at those times cellular defects of immunity had not been excluded these now seem a more probable explanation in many cases (H4, Nl). 

This serum immunoglobulin pattern has been associated with proven antibody deficiency (C4). The five recorded patients were all boys (B27, D2, SI). Two parents had IgM deficiency, and one boy in a sibship suggestive of Bruton s disease. 

Sohaller, J., Davis, S. D., Ching, Y.-C., Lagunoff, D., Williams, C. P. S., and Wedgwood, R. J., Hypergammaglobulinemia, antibody deficiency, autoimmune haemolytic anaemia and nephritis in an infant with a familial lymphopenic immune defect. Lancet ii, 825-829 (1966). 

Stoelinga, G. B. A., van Muster, P. J. J., and Slooff, J. P., Antibody deficiency syndrome and autoimmune haemolytic anaemia in a boy with isolated IgM deficiency. Dysimmunoglobulinaemia Type 5. Acta Paediat. Scand. 58, 352-362 (1969). 

Meth MJ, Rosenthal DW, Bonagura VR. Subcutaneous immunoglobulin infusion to treat infants and toddlers with antibody deficiencies. Ann Allergy Asthma Immunol 2010 105(2) 187-8. 

Two adults with pre-existing primary antibody deficiencies developed recurrent infections immediately after receiving rituximab for refractory idiopathic thrombocytopenic purpura [161 ]. The temporal relation between rituximab administration and the onset of infection suggested that rituximab accelerated immune deficiency in these patients. 

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