Using Antibodies in Immune Deficiency Treatment

Antibodies or immunoglobulins can be used in the treatment of immune deficiency disorders. This branch of science is called immunoglobulin therapy, which is the centerpiece of immune deficiency treatment because it remarkably lowers both the severity and frequency of infections. 

Immunoglobulins

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Overview of immunoglobulin therapy

The preparations of therapeutic immunoglobulins, which are blood products sourced from many healthy donors, are consisted of almost only IgG. Yet, trace amounts of IgM and IgA can also be found in commercially available products. Patients with immunodeficiency disorders, who have a natural problem in producing robust, protective antibodies, need routine immunoglobulin administration.

Immunoglobulin therapy aims to provide sufficient and functional serum IgG levels comparable to what is found in normal subjects to be able to neutralize and protect against infectious pathogens such as parasites, viruses, and bacteria. Much higher immunomodulating doses of immunoglobulin are sometimes administered for inflammatory and autoimmune conditions.

Although some of these underlying immunomodulating mechanisms have been deciphered, there are still undiscovered mechanisms and ongoing studies are performed to elucidate these.

Immunoglobulins in immune deficiency treatment

X-linked agammaglobulinemia (XLA), which is an antibody deficiency occurred by a gene mutation for Bruton’s tyrosine kinase leading to striking insufficiency of the production of B cells and agammaglobulinemia, could be controlled by immunoglobulin replacement that can prevent infections and allow patients to lead productive and healthy lives.

Without appropriate therapy, patients with XLA suffer from severe infectious morbidity. All XLA patients have to take replacement immunoglobulin therapy as a life-long treatment regardless of the timing of diagnosis or initiation. In special circumstances of XLA, such as those with persistent bacterial infections, bronchiectasis, and nonbacterial infections, larger amounts of immunoglobulins may be used.

Common variable immunodeficiency (CVID), which is characterized by hypogammaglobulinemia (low levels of two out of three major isotypes) with nonprotective antibody actions against pathogens, may be used in conjunction with prophylactic antibiotics.

Once CVID is diagnosed, immunoglobulin therapy should be started because recurrent infections can result in bronchiectasis and exacerbating pre-existing conditions. In special circumstances of CVID such as persistent bacterial infections and bronchiectasis, larger doses of immunoglobulins can be used.

A deficiency of one or more of the four IgG subclasses (IgG1, IgG2, IgG3, and IgG4) with a normal total IgG level is called IgG subclass deficiency. A history of recurrent sinopulmonary infections is usually the main symptom of IgG subclass deficiency, but other more serious infections can be also seen. Immunoglobulin therapy can only be taken if there is a remarkable antibody dysfunction.

This may be attributed to the fact that checking of serum of patients and detection of low levels of one or more IgG subclasses cannot be applied to evaluate biological relevance because compensating antibodies to different pathogens can be contained in any of the isotypes.

Selective IgA deficiency, which is considered to be the most common primary immunodeficiency, is caused by a decreased level of serum IgA in the presence of normal levels of serum IgM and IgG. Not all patients with selective IgA deficiency experience symptoms or health issues. Asymptomatic patients with selective IgA deficiency do not require immunoglobulin therapy because they don’t suffer from prominent symptoms or health issues.

Most patients with IgA deficiency, who suffer from allergic disorders, recurrent infections, and autoimmune disorders, should be treated with prophylactic antibiotics, and immunoglobulin therapy may be only administered in severely ill patients when concomitant findings (such as a specific antibody defect) are found.

Hyper IgM syndromes (HIGM) are characterized by normal or high levels of IgM with low or absent IgG, IgA, and IgE. Malfunctioning T-cells can also be detected in HIGM. Patients with HIGM may develop cytopenias, chronic diarrhea, and liver disease.

Regardless of all HIGM forms, immunoglobulin therapy should be administered as a way to decrease the severity and rate of infections.

In conclusion, immunoglobulin therapy is indicated in the setting of primary immunodeficiency affecting antibody production such as XLA, CVID, HIGM as it notably reduces both the severity and frequency of infections occurred in immune deficiency disorders.

References

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  • Chapel, H., and Cunningham‐Rundles, C., 2009. Update in understanding common variable immunodeficiency disorders (CVIDs) and the management of patients with these conditions. British journal of haematology, 145(6), pp.709-727.
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  • Quartier, P., Debré, M., De Blic, J., de Sauverzac, R., Sayegh, N., Jabado, N., Haddad, E., Blanche, S., Casanova, J.L., Smith, C.E. and Le Deist, F., 1999. Early and prolonged intravenous immunoglobulin replacement therapy in childhood agammaglobulinemia: a retrospective survey of 31 patients. The Journal of pediatrics, 134(5), pp.589-596.
  • Sandomenico, A., Severino, V., Chambery, A., Focà, A., Focà, G., Farina, C., and Ruvo, M., 2013. A comparative structural and bioanalytical study of IVIG clinical lots. Molecular biotechnology, 54(3), pp.983-995.
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Further Reading

Last Updated: Sep 11, 2020

Dr. Ahmed Donia

Written by

Dr. Ahmed Donia

Since his early childhood, Ahmed has such an inquisitive mind that cannot stop searching for answers. His mind has always been skeptic and questionable. He has never been satisfied with simple answers such as “Yes” or “No”. Ahmed has a BSc in Pharmaceutical Sciences and an MSc in Microbiology. Currently, he is a Ph.D. candidate in Microbiology and Immunology.

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