Primary immunodeficiencies

Primary immunodeficiencies are uncommon, and may occur in 1 in 10,000 individuals (6). Many primary immunodeficiencies are hereditary and congenital, and first appear in infants and children. Primary immunodeficiencies are classified into four main groups (7) relating to the lymphocytes (B-ceUs, T-ceUs, or both), phagocytes, or the complement cascade (8). Primary deficiency diseases result from B-ceU defects in 50% of cases, from T-ceU defects in ca 10%, and from combined B- and T-ceU defects in ca 20%. Phagocytic disorders account for 18% and complement defects occur in 2% of all cases. 

Gallimore, C. I., Taylor, C., Gennery, A. R., Cant, A. J, Galloway, A., Iturriza-Gomara, M., and Gray, J. J. (2006). Environmental monitoring for gastroenteric viruses in a pediatric primary immunodeficiency unit. /. Clin. Microbiol. 44,395-399. 

Primary immunodeficiency states Hepatitis A exposure Hepatitis A prophylaxis... 

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

In addition, we discuss the most likely clinical consequences of mild-to moderate immunosuppression and potential confounders as well as non-immune factors that may modify these disease outcomes. Cases of profound immunosuppression, such as primary immunodeficiency diseases or HIV/AIDS, are not discussed, as these represent extreme examples of immunosuppression where neither the specific clinical diseases nor the eventual outcomes have much in common with events that occur in individuals with mild-to-moderate immunosuppression. 

In contrast to profound immunosuppression, such as that which occurs in patients with HIV/AIDS or primary immunodeficiency diseases, exposure to immunotoxic chemicals or drugs is believed to be more likely to cause mild-to-moderate levels of immunosuppression (e.g., a 20% decrease in white blood cell counts). This review attempts to address, both qualitatively and quantitatively, the potential adverse health effects of moderate levels of immunosuppression. The following general conclusions can be surmised. 

Considerable data is available suggesting thatmild-to-moderate immunosuppression can lead to an increase in infectious disease. The types of infections that occur tend to result from either common pathogens (e.g., causing upper respiratory tract infections) or latent viruses (e.g., herpes cold sores), rather than opportunistic organisms such as Pnuemocyctis carinii. These are usually not life-threatening, except in certain susceptible populations, such as the elderly. Opportunistic infections, in contrast, are more prevalent in individuals where severe forms of immunosuppression are present, such as primary immunodeficiency diseases or HIV/AIDS. 

Immunodeficiency 100-200 mg/kg/mo IV at 0.01-0.04 mL/kg/min to 400 mg/kg/dose max UP 400 mg/kg/dose IV daily x 5 d BMP 500 mg/kg/wk X in renal insuff Caution [C, ] Separate administration of live vaccines by 3 mo Contra IgA deficiency w/ Abs to IgA, severe thrombocytopenia or coagulation disorders Disp Inj SE Associated mostly w/ inf rate GI upset Interactions X Effects OF live virus vaccines EMS May cause anaphylactic Rxn OD Unlikely Immune Globulin, Subcutaneous (Vivaglobin) [Immune Serum] Uses Primary immunodeficiency Action IgG supl Dose 100—200 mg/kg BW subq wkly abd, thighs, upp arms, or lat al hip Caution [C, ] Contra Hx anaphylaxis to immune globulin some IGA deficiency Disp Inj SE Inj site Rxns, HA, GI complaint, fevCT, N, D, rash, sore throat EMS May be self administered at home may cause anaphylactic Rxn OD Unlikely to cause life-threatening Sxs... 

Primary immunodeficiency diseases (PIDs) are defects of the immune system that are due to genetic abnormalities or some failure in normal embryological development. They are usually apparent at birth or develop shortly thereafter. Approximately 70 PIDs have been described, including those specihc for humoral immunity (e.g., X-linked agammaglobulinemia, immune globulin [Ig] A dehciency), cellular immunity (e.g., DiGeorge s syndrome), or both (e.g., severe combined immunodehciency syndrome). 

D) A primary immunodeficiency disease that is blocking the maturation of B cells into plasma cells... 

D. The boy has significantly reduced serum antibody levels and a reduced ability to mount an antibody response to childhood vaccinations. The most probably cause is a primary immunodeficiency disease affecting humoral immunity. 

Yin EZ, Frush DP, Donnelly LF, and Buckley RH. Primary immunodeficiency disorders in pediatric patients Clinical features and imaging findings. Am J Roentgenol 2001 176 1541-1552. 

Keerthikumar, S., Raju, R., Kandasamy, K., Hijikata, A., Ramabadran, S., Balakrishnan, L., Ahmed, M., Rani, S., Selvan, L.D.N., Somanathan, D.S., et al, (2008) RAPID Resource of Asian Primary Immunodeficiency Diseases. Nucl Acids Res, 37, D863-D867. 

H. Other considerations Proleukin has been designated an orphan drug for use in the treatment of metastatic renal cell carcinoma, metastatic melanoma, non-Hodgkin s lymphoma, and primary immunodeficiency disease associated with T-cell defects. 

Treatment of primary immunodeficiency states in which severe impairment of antibody forming capacity idiopathic thrombocytopenic purpura (IPT) bone marrow transplantation pediatric HIV infection... 

Berger M Principles of and advances in immunoglobulin replacement therapy for primary immunodeficiency. Immunol Allergy Clin North Am 2008 28 413. [PMID 18424340]... 

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

Primary immunodeficiency diseases An experimental model for molecular medicine. Fischer, A. (2001). Lancet, 357 (9271) 1863-1869. 

Human Immune globulin Venoglobulin-S (Alpha Therapeutics) Primary immunodeficiencies idiopathic thrombocytopenic purpurea Kawasaki disease... 

In 14 patients with primary immunodeficiency disease, progressive neurodegeneration occurred and a possible relation to immunoglobulin therapy could not be ruled out (57). 

Intravenous immune globulin (IVIG) Human IgG - Primary immunodeficiency syndromes - Kawasaki disease - Acute renal failure 103,106-108... 

Slatter MA, Gennery AR (2010) Primary immunodeficiencies associated with DNA-repair disorders. Expert Rev Mol Med 12 e9... 

Chapel HM. Safety and availability of immunoglobulin replacement therapy in relation to potentially transmissable agents. lUIS Committee on Primary Immunodeficiency Disease. International Union of Immunological Societies. Clin Exp Immunol 1999 118 29-34. 

Many primary immunodeficiency syndromes in which genetic defects are known or suggested are associated with a variety of autoimmune manifestations. A selection of immunodeficiencies together with their associated autoimmune manifestations is shown in Table 2. Immune dysregulation, persistent antigen stimulation, recurrent tissue damage, and defective clearance of immune complexes are pathogenetic factors that may lead to autoimmunity in immuno-deficient individuals (Etzioni, 2003). 

The most common primary immunodeficiency syndromes are selective IgA deficiency (SIgAD) and common variable... 

Selective IgA deficiency (SIgAD). The most common form of primary immunodeficiency. Autoimmunity is the most prevalent manifestation of this deficiency. Individuals with SIgAD have an increased risk of developing systemic (e.g. systemic lupus... 

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