New diagnostic criteria for CVID

Figures & data

Table 1. Proposed diagnostic criteria for common variable immune deficiency.

A	Must meet all major criteria
	Hypogammaglobulinemia IgG <5 g/l [4] No other cause identified for immune defect [7] Age >4 years [6]
B	Sequelae directly attributable to immune system failure (one or more)
	Recurrent, severe or unusual infections Poor response to antibiotics Breakthrough infections in spite of prophylactic antibiotics Infections in spite of appropriate vaccination, for example, HPV disease Bronchiectasis and/or chronic sinus disease Inflammatory disorders or autoimmunity [9]
C	Supportive laboratory evidence (three or more criteria)
	Concomitant reduction or deficiency of IgA (<0.8 g/l) and/or IgM (<0.4 g/l) [10,11] Presence of B cells but reduced memory B cell subsets and/or increased CD21 low subsets by flow cytometry [12] IgG3 deficiency (<0.2 g/l) [13,14] Impaired vaccine responses compared with age-matched controls [15] Transient vaccine responses compared with age-matched controls [3] Absent isohemagglutinins (if not blood group AB) [16] Serological evidence of significant autoimmunity, for example, Coombes test Sequence variations of genes predisposing to CVID, for example, TACI, BAFFR, MSH5, etc. [17,18]
D	Presence of relatively specific histological markers of CVID (not required for diagnosis but presence increases diagnostic certainty)
	Lymphoid interstitial pneumonitis [19] Granulomatous disorder [20,21] Nodular regenerative hyperplasia of the liver [22,23] Nodular lymphoid hyperplasia of the gut [24] Absence of plasma cells on gut biopsy [25,26]

Meeting criteria in Categories ABC or ABD indicate probable CVID. Patients meeting criteria ABC and ABD should be treated with intravenous immunoglobulin/subcutaneous immunoglobulin (Figure 1). Patients meeting criteria A alone, AB or AC or AD but not B, are termed possible CVID. Some of these patients may need to be treated with intravenous immunoglobulin/subcutaneous immunoglobulin. Patients with levels of IgG >5 g/l, not meeting any other criteria, are termed hypogammaglobulinemia of uncertain significance (HGUS).

CVID: Common variable immune deficiency.

Figure 1. Diagnostic and treatment algorithm for common variable immune deficiency. Patients must meet all major criteria in Category A for consideration of CVID. Category B confirms the presence of symptoms indicating immune system failure. To have probable CVID, patients must also have supportive laboratory evidence of immune system dysfunction (Category C) or characteristic histological lesions of CVID (Category D). Patients with mild hypogammaglobulinemia (IgG >5 g/l) are termed hypogammaglobulinemia of uncertain significance (HGUS). Patients meeting Category A criteria but not other criteria are deemed to have possible CVID. Most patients with probable CVID are likely to require IVIG/SCIG. Some patients with possible CVID will require IVIG/SCIG, but most patients with hypogammaglobulinemia of uncertain significance are unlikely to need IVIG/SCIG replacement.

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