CVID- Major features

1
CVID- Major features

• Recurrent pyogenic infections, with onset at any
  age
• Increased incidence of autoimmune disease
• Total immunoglobulin level lt 300 mg/dL ,with IgG
  level lt 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 defectT cell defectActivation 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 -gt 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 DefectOverabundance -gt
  lymphokines suppressing immunoglobulin synthesis
  (g-INF)
• Activation Defect ? CD40 ligand (gp39) mRNA and
  functional protein in 40 patients
• Genetic AbnormalityHLA 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 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
9234-48)
10
Autoimmunity (n248)

• AITP 15 AIHA 12RA 5JRA 4Anti
  -IgA 7SS 2PBC 3Pernicious
  anemia 3Hyperthyroid disease 2SLE 2Vascu
  litis 3 autoimmune diseases 56