Table 2 New diagnostic criteria for CVID

A. Must meet all major criteria

❖ Hypogammaglobulinemia: IgG below 5 g/L for adults

❖ No other cause identified for immune defect

❖ Age > 4 years

B. Clinical sequelae directly attributable to in vivo immune system failure (ISF) (1 or more criteria)

❖ Recurrent, severe or unusual infections.

❖ Poor response to antibiotics

❖ Breakthrough bacterial infections in spite of prophylactic antibiotics

❖ Infections in spite of immunization with the appropriate vaccine e.g. HPV disease

❖ Bronchiectasis and/ or chronic sinus disease

❖ Inflammatory disorders or autoimmunity

C. Supportive laboratory evidence (3 or more criteria)

❖ Concomitant deficiency or reduction of IgA (< 0.8 g/l) and/or IgM (< 0.4 g/l)

❖ Presence of B cells but reduced memory B cell subsets and/or increased CD21 low subsets by flow cytometry

❖ IgG3 deficiency (< 0.2 g/l)

❖ Impaired vaccine responses compared to age-matched controls

❖ Transient responses to vaccines compared to age-matched controls

❖ Absent isohemagglutinins (if not blood group AB)

❖ Serological support for autoimmunity in section B e.g. positive Coombs test

❖ Sequence variations of genes predisposing to CVID e.g. TACI, BAFFR, MSH5 etc

D. Presence of any one of relatively specific histological markers of CVID (Not required for diagnosis but presence increases diagnostic certainty)

❖ Lymphoid interstitial pneumonitis

❖ Granulomatous disorder

❖ Nodular regenerative hyperplasia of the liver

❖ Nodular lymphoid hyperplasia of the gut

❖ Absence of plasma cells on gut biopsy