1. 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

2. 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

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

4. 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

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

6. 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

7. Clinical Manifestations
Infections
Autoimmunity
Gastrointestinal disease
Lymphoproliferative disorders
Granulomatous disease

8. 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

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

10. Autoimmunity (n=248)
AITP AIHA RA JRA Anti-IgA SS PBC Pernicious anemia 3 Hyperthyroid disease 2 SLE Vasculitis autoimmune diseases 56