Common Variable Immunodeficiency in Adults

Dr Ajay Wanchu, MD, DM (Clinical Immunology) PGIMER, Chandigarh India

Objective
To review the causes of primary immunodeficiency among adults To have an overview of common variable immunodeficiency

Primary Immunodeficiency in Adults

Adult onset common Common variable immunodeficiency IgA deficiency Complement deficiency Delayed presentation of a childhood disorder ADA deficiency WAS CGD Childhood disorder with survival into adulthood CVID, IgA deficiency, XLA, CGD, WAS, LAD deficiency, Hyper-IgM syndrome

Common Variable Immunodeficiency

Heterogeneous group of immunological disorders, unknown etiology, levels of serum Igs and impaired antibody responses 1: 10,000 to 50,000 Sex: equal Age: Bimodal: 6-10 & 20-30 yrs

Clinical Presentations
ed susceptibility to infections recurrent, severe, opportunistic Autoimmune diseases - AITP, AIHA, RA, SLE, etc Inflammatory disorders - IBD, sarcoidosis

Profile of Infections (%)

Recurrent bronchitis, sinusitis, otitis Pneumonia Viral Hepatitis H/O severe Herpes zoster Giardia enteritis Pneumocystis carini infection Mycoplasma pneumonia 98 76.6 6.6 3.6 3.2 2.8 2.4

Chronic Mucocutaneous candidiasis, Salmonella diarrhea, Campylobacter enteritis, Osteomyelitis, Septic arthritis, Nocardia brain abscess, etc.

Autoimmunity (n=248)
AITP AIHA RA JRA Anti-IgA SS PBC Pernicious anemia Hyperthyroid disease SLE Vasculitis autoimmune diseases 15 12 5 4 7 2 3 3 2 2 365 56

Malignancy
NHL 7.7% - mostly extranodal, all B cell type Others Waldenstroms macroglobulinemia Hodgkins disease Adenocarcinoma - stomach, ovary, colon Sq cell Ca - vagina, skin, mouth, lung Ca - breast, prostate Melanoma

GI Diseases (n=248*)
Nodular lymphoid hyperplasia UC Ulc. Proctitis Crohns disease Malabsorption, no other diag. Giardiasis Malnutrition needing TPN Campylobacter enteritis *Clin Immunol 1999; 92:34-48 10 4 3 9 10 8 5 5

Laboratory Abnormalities
IgG, mostly with IgA and IgM Lymphopenia 20% B cell numbers - mostly normal CD4/CD8 ratios, in CD4+CD45+ T cells levels of IL-4, IL6, soluble CD8, CD25, 2microglobulin, HLA-DR, LFA-3 and ICAM-1 : secondary to infections 60% - ed proliferative responses to TCR stimulation and ed induction of gene expression for IL-2, IL-4, IL-5 and IFN-

Family Members
10% of patients - CVID or IgA deficiency is seen in more than one family member More likely to have IgA deficient children Possible linkages to HLA Class II or III genes

Differential Diagnosis
Hypogammaglobulinemia secondary to other disorders e.g. secondary to loss of Ig and other serum proteins in the urine & stool CLL, thymoma, other lymphoreticular malignancies Secondary to other drugs like phenytoin, cyclophosphamide Other primary immunodeficiency diseases e.g. XLA

Mortality and Survival

Cunningham-Rundes and Bodian (Clin Immunol 1999; 92:34-48)
248 patients; median follow-up 7 yrs (0-25) 57 died from 1-32 yrs after diagnosis, ages 5-90 yrs (median age 43) - 27% Causes -Lymphoma, cor pulmonale, hepatitis, malnutrition, other malignancies, vasculitis, etc. Poor prognostic signs: % of peripheral B cells, PHA response, initial IgG level For each % in B cell numbers, risk of death on follow-up ed by a factor of 0.92

Treatment
Early and aggressive antibiotic therapy, ongoing therapy for autoimmune and inflammatory disorders & surveillance for malignancy Replacement with IVIG: 400-500 mg/kg/month Prevents breakthrough infections, abnormal pulmonary function may improve, even if chronic lung damage is present