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Table 1. Genetic Defects in Common Variable Immunodeficiency

Genetic defect	Chromosomal location	Inheritance	Phenotype	B cells
TNFRSF13B (TACI); approximately 10% of cases	17p11.2	Autosomal dominant (AD)	Common variable immunodeficiency, selective immunoglobulin A deficiency (SIgAD)	< 5% of cases involve absent TACI expression; 95% of cases have normal TACI expression on B cells; low-to-absent IgA levels; autoimmune disease; lymphoproliferative disease; splenomegaly; reduced class-switched memory B cells
TNFRSF13C (BAFF-R); < 1% of cases	22q13.2	Autosomal recessive (AR)	Late-onset, incomplete penetrance	Absent BAFF-R on B-cell surface; reduced class-switched and non–class-switched memory B cells; increased transitional B cells; impaired response to polysaccharide antigen
ICOS; approximately 2% of cases	2q33	AR	Early and late onset	Absent ICOS on activated T cells; reduced class-switched memory B cells; nodular lymphoid hyperplasia; autoimmunity; predisposition to neoplasm
CD19; < 1% of cases	16p11.2	AR	Early and late onset	Low-to-absent CD19 on B cells; reduced class-switched memory B cells; low CD21+ expression on B cells; normal number of CD20+ cells in peripheral blood
CD81; < 1% of cases		AR	Unclear	Impaired Ca⁺⁺ flux after BCR stimulation; autoimmunity; impaired response to protein and polysaccharide antigens; nearly absent CD19 expression
CD20; < 1% of cases		AR	Unclear	Reduced switched memory B cells; impaired somatic hypermutation; impaired response to pneumococcal polysaccharide antigens
CD21; < 1% of cases		AR	Unclear	Reduced class-switched memory B cells; hypogammaglobulinemia; reduced binding of C3d-containing immune complexes and EBV-gp350 to B cells; impaired response to pneumococcal polysaccharide antigens

Table.

Brand (Manufacturer)	Virus Inactivation process	pH; Additives *	Osmolality (mOsm/kg)	Parenteral Form & Final Concentrations	IgA Content µg/ml	Route of administration
Bivigam (Biotest Pharmaceuticals)	Cold ethanol fractionation, solvent/detergent, nanofiltration	4.0-4.6; glycine, polysorbate 80	Unspecified	Liquid 10%	< 200 µg/ml	IV
Flebogamma DIF(Grifols)	Pasteurization, solvent/detergent treatment, nanofiltration, low pH treatment	5.1-6; D-Sorbitol	240-370	Liquid 5%, 10%	< 50 µg/ml in 5% solution, < 100 µg/ml µg/ml in a 10% solution	IV
Gammagard S/D Low IgA (Baxter)	Cold ethanol fractionation, solvent detergent (S/D) treatment	6.4-7.2;Albumin,Glycine,Glucose, PEG, tri-n-butyl phosphate, octoxynol, polysorbate 80	5%: 636; 10%:1250	Lyophilized powder5%, 10%	< 1 µg/ml in a 5% solution	IV
Gammaplex(Bio Products)	Solvent/detergent, nanofiltraion, low pH incubation	4.8-5.1; D- sorbitol, glycine, polysorbate 80	420-500	Liquid 5%	< 10 µg/ml	IV
Octagam (Octapharma)	Cold ethanol fractionation, solvent/detergent, pH4 treatment	5.1-6.0;maltose	310-380	Liquid 5%	< 200 µg/ml	IV
Privigen(CSL Behring)	pH 4 incubation, nanofiltration, depth filtration	4.6-5.0;L-proline	240-440	Liquid 10%	< 25 µg/ml	IV
Gammagard Liquid(Baxter)	Solvent detergent (S/D), nanofiltration, low pH incubation at elevated temp	4.6-5.1; Glycine	240-300	Liquid 10%	37 µg/ml	IV or Subcutaneous
Gamunex-C(Grifolis)	Caprylate precipitation, depth filtration, chromatography, pH 4 incubation	4-4.5; Glycine	258	Liquid 10%	46 µg/ml	IV or Subcutaneous
Gammaked (Kedrion Biopharma)	Caprylate precipitation, depth filtration, chromatography, low pH incubation	4.0-4.5; glycine	258	Liquid 10%	46 µg/ml	IV or Subcutaneous
Cuvitru (Shire)	Fractionation, SD treatment, nanofiltration, low pH treatment	4.6-5.1; glycine	280-292	Liquid 20%	80 µg/ml	Subcutaneous
Hizentra (CSL Behring)	Cold alcohol freactionation, octanoic acid fractionation, and anion exchange chromatography	4.6-5.2; L-proline, polysorbate 80	380	Liquid 20%	< 50 µg/ml	Subcutaneous
HyQvia (Baxter Healthcare)	Solvent/detergent, nanofiltration, lowpH incubation	4.6-5.1; recombinant human hyaluronidase (7.4)	240-300 (recombinatnt human hyaluroidase (290-350)	Liquid 10%	37 µg/ml	Subcutaneous

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