CVID- Major features Recurrent pyogenic infections, with onset at any age Increased incidence of autoimmune disease Total immunoglobulin level < 300 mg/dL ,with IgG level < 250 mg/dL B cell numbers usually normal

CVID Commonest symptomatic primary antibody deficiency Heterogenous group of immunological disorders, decrease serum Ig and antibody response Prevalence: 1/50,000 – 1/100,000 Occur in any age Sex: equal

Etiology B lymphocytes unable to differentiate into plasma cells B cell defect T cell defect Activation defect

B Cell Defect CVID B cell : phenotypic characteristics of immature B cell CVID B cell+ normal T cell / CVID T cell + normal B cell CVID B cell + mitogen + soluble T cell factors Lack of external stimuli -> maturation arrest at immature B cell

T Cell Defect 25-30% patients  CD4/CD8 ratio  IL-2, IL-4, IL-5, INF-g Decreased proliferation to mitogen

Suppressor T Cell Defect Overabundance -> lymphokines suppressing immunoglobulin synthesis (g-INF) Activation Defect  CD40 ligand (gp39) mRNA and functional protein in 40% patients Genetic Abnormality HLA class III region , between C4B and C2 genes

Clinical Manifestations Infections Autoimmunity Gastrointestinal disease Lymphoproliferative disorders Granulomatous disease

Infections Recurrent bacterial infection caused by encapsulated bacteria, Streptococcus pneumoniae, Haemophilus influenzae, Staphylococcus aureus Bordetella pertussis important in childhood Frequent complication: chronic sinusitis and bronchiectasis Fungus, mycbacteria, Pneumocystis carinii : rare Enteroviral meningoencephalitis : echovirus-11

Profile of Infections (%) Recurrent bronchitis, sinusitis, otitis 98 Pneumonia 76.6 Viral Hepatitis 6.6 H/O severe Herpes zoster 3.6 Giardia enteritis 3.2 Pneumocystis carini infection 2.8 Mycoplasma pneumonia 2.4 Chronic Mucocutaneous candidiasis, Salmonella diarrhea, Campylobacter enteritis, Osteomyelitis, Septic arthritis, Nocardia brain abscess, etc. Cunningham-Rundes and Bodian (Clin Immunol 1999; 92:34-48)

Autoimmunity (n=248) AITP 15 AIHA 12 RA 5 JRA 4 Anti-IgA 7 SS 2 PBC 3 Pernicious anemia 3 Hyperthyroid disease 2 SLE 2 Vasculitis 3 autoimmune diseases 56