VIMS Journal: July 2016

Review Article

Primary Immuno-Deficiency Disorder

Dr. Tapabrata Chatterjee, Dr. Ajanta Haldar, Dr. Suparna Guha

Introduction :
Primary immunodeficiency disorder is rare when considered individually. However taken together as a group, they represent a significant health problem with a frequency compatible to disorders such as cystic fibrosis and childhood leukemia.[1] Clinical indicators of primary immunodeficiency states, includes infections with opportunistic organisms, unusual infections or severe infections with organisms of low pathogenicity, infections failing to respond to appropriate therapy, persistence of infection beyond what is expected, family history of immunodeficiency and dysmorphic feature suggestive of syndromes associated with immunodeficiency.[2]

Key Words :
Antibody Deficiency, Phagocytic defects, Immune dysregulation, Primary immunodeficiency disorders, Severe combined immunodeficiency (SCID).

Classification and Manifestation :
Immunodeficiency disorders can be broadly classified into:
A) B-cell and immunoglobulin deficiency
B) T- Cell Deficiency
C) Deficiency in phagocytosis
D) Compliment deficiency
B- cell deficiency generally presents around 6 months of age with respiratory, GIT infection, skin, sepsis and meningitis. The common organisms responsible are gram+ve encapsulated bacteria, micoplasma and echovirus.

T-cell deficiency presents early with systemic GIT and respiratory infections. The organisms responsible are viruses, pyogenic bacteria, fungi, protozoa and mycobacterium.

The defect in the phagocytic system represents with skin infection, lymphadenitis, abscesses, gastro-intestinal manifestations, osteo-myelitis and septic arthritis. The common organisms are staphylococcus, gram -ve bacteria and fungi. Though the presentation may be early, recognition as an immunodeficiency disorder may be late.

Compliment deficiency presents systemic bacterial infection, commonly as recurrent infection by common and uncommon strains of Neisseria meningitis.[2,3,4]

Common Immunodeficiency Disorder :
l. Severe Combined Immunodeficiency :

The presentation of SCID can be early with significant bacterial infections, pneumocystis carnii pneumonia and disseminated BC Geosis. The children with this disorder fail to thrive, have persistent diarrhoea, respiratory infection and thrush. The disorders are characterised by defects in both T & B lymphocytes. Early treatment of infections with antibiotics and early institution of immunoglobulin therapy improves the prognosis. Bone marrow transplantation is the only curative treatment.[5]

2. Panhypogamma Globulinemia :
It presents as a X-linked recessive disorder and male infants presents in the first two years of life. Extracellular bacteria are the usual pathogens but severe enteroviral infections are also common. Arthritis affecting large joints is the common manifestation apart from overwhelming sepsis. Tonsillar tissue and lymph nodes are conspicuously unremarkable and all types of immunoglobulin are either absent or present well below the age appropriate normal range. Treatment includes administration of gamma globulins periodically and aggressive treatment with antibiotics for infections.[6]

3. Selective IgG Subclass Deficiency :
Though IgG subclass deficiency is of no clinical relevance in vast majority, children with low or absent IgG2 subclass can be symptomatic. There can be coexistent IgA subclass deficiency in some of these children.[6]

4. Selective IgA Deficiency :
IgA are as common as 1 in 400 in Caucasian population and most often are not identified as the infections are often trivial. However, patients with IgA deficiency may have recurrent sino-pulmonary infections and can present autoimmune diseases.[2, 4]

5. Common Variable Immunodeficiency :
The genetic defects underlying this group of disorders are largely unknown. It presents with manifestation of predominantly B-cell defect and minimum T-cell defect. The onset of clinical manifesatins, are late with sinopulmonaryinfectionand malabsorption.[2]

6. Chronic Granulalomatous Disease :
Chronic granulomatous disease is the most common inherited disorder of phagocyte function presenting as a x-linked or autosomal recessive state. In chronic granulomatous disease, there is failure of production of superoxide radical important for killing phagocytosed bacteria. Children present with lymphadenopathy, hepatosplenomegaly, pneumonia, including abcesses in unusual site, osteomyelitis and dermatitis. Intestinal granuloma formation may mimic inflammatory bowel disease. The prognosis is guarded and even bone marrow transplant, have limited success.[2]

7. Hyper IgM Syndrome :
Hyper IgM syndrome is X-linked disorder due to defect in the CD40 ligand gene. CD40 ligand found on T cells interacts with CD40 on Bcells, promoting their growth and differentiation as well as for isotope switching. Failure of this important signal leads to increased number of B-Cells producing normal or increased quantities of IgM but no IgG, IgA or IgE.[7, 8]

8. Compliment and Associated Disease :
Most children with compliment deficiency has increased susceptibility infection and there is a higher incidence of autoimmune disorder, perhaps because of failure to adequately clear circulating immune complexes. Defciencies of individual components can be detected by immuneassays using specific antiserum. However, screening can be done by CH50 assay for the classical pathway and AP50 for the alternate pathway.[9]

9. Wiskott Aldrich Syndrome :
Both B & T cell lines are affected in this Xlinked disorder. Lymphopenia elevated IgE and IgA and low IgM leads to frequent infections with capsulated and non capsulated bacteria and viruse. Autoimmune disease, eczema and increased incidence of malignancy especially Epstein Barr, associated malignancies like lymphoma and brain tumour is common.[2]

10. Di George Syndrome :
Di George syndrome consists of conotruncal cardiac defects, immunodeficiency secondary to thymic aplasia and hypocalcaemia, commonly known as Catch 22 syndrome. As there is impairment in T cell number and functions, there is increased susceptibility to viral and candida infections. There is also increased incidence of auto-immune disorder, which presents at an older age. Bone marrow transplant and Thymus transplant can be often curative.[2]

Conclusion :
Early suspicion of primary immunodeficiency disorders lead to earlier diagnosis, accurate determination of diseases outcome s, appropriate genetic and family counselling, better insight of management strategies and potential cures for some. Future research is directed towards delineation of gene identification of new unrecognised immunodeficiency disorders and development of new strategies like gene therapy.

  1. Al-Herz W, Bousfiha A, Casanova JL, Chapel H, Conley ME, Cunningham-Rundles C, et al. Primary immunodeficiency diseases: an update on the classification from international Union of Immunological Societies Expert Committee for Primary Immunodeficiency. Frontiers in Immunology. 2011;2:54.

  2. Piquet D, Tosi C, Luthi JM, Andresen I, Juge O. Redimune ((R)) NF Liquid, a ready to use, high concentration intravenous immunoglobulin therapy preparation, is safe and typically well tolerated in the routine clinical management of a broad range of conditions. Clin Exp Immunol. 2008;152:45-9.

  3. Notarangelo LD, Forino C, Mazzolari E. Stem cell transplantation in primary immunodeficiencies. Curr Opin Allergy Clin Immunol. 2006;6:443-8.

  4. Subbarayan A, Colarusso G, Hughes SM, Gennery AR, Slatter M, Cant AJ, et al. Clinical features that identify children with primary immunodeficiency diseases. Pediatrics. 2011;127:810-6.

  5. Slatter MA, Gennery AR. Clinical immunology review series: an approach to the patient with recurrent infections in childhood. Clin Exp Immunol. 2008;152:389-96.

  6. Winkelstein JA, Marino MC, Ochs H, Fuleihan R, Scholl PR, Geha R, et al. The X-linked hyper- IgMsyndrome: clinical and immunologic features of 79 patients. Medicine (Baltimore). 2003;82:373-84.

  7. Berrington JE, Flood TJ, Abinum M, Galloway A, Cant AJ. Unsuspected Pneumocystis carinii pneumonia at presentation of severe primary immunodeficiency. Arch Dis Child. 2000;82:144-7.

  8. Bouma G, Ancliff PJ. Thrasher AJ, Burns SO. Recent advances in the understanding of genetic defects of neutrophil number and function. Br J Haematol. 2010;151:312-26.

  9. Wood P, Stanworth S, Burton J, Jones A, Peckham DG, Green T, et al. UK Primary Immunodeficiency Network. Recognition, clinical diagnosis and management of patienys with primary antibody deficiencies: a systematic review. Clin Exp Immunol. 2007; 149:410-23.


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