# Demographic, clinical, and immunological features in combined immunodeficiency patients: a comparative analysis of those with and without pulmonary manifestations – a multicenter study from Iran

## TL;DR

This study compares clinical and immunological features of combined immunodeficiency patients in Iran, focusing on those with and without lung issues.

## Contribution

Identifies a prognostic triad of low platelets, IgG, and IgE for mortality in CID patients with pulmonary manifestations.

## Key findings

- 81.1% of Iranian CID patients had pulmonary manifestations detected via HRCT.
- Patients with lung abnormalities had significantly lower CD4+ T-cell and CD19+ B-cell counts.
- Low baseline platelets, IgG, and IgE were strongly associated with higher mortality rates.

## Abstract

Combined immunodeficiency (CID) involves profound defects in B and T lymphocyte development and function. This study examined clinical and immunological phenotypes of CID patients with and without pulmonary manifestations.

This retrospective multicenter study included 53 CID patients diagnosed between 2009 and 2022 with available thoracic computed tomography scans. Patients were categorized based on pulmonary manifestations presence. Demographic, clinical, and laboratory characteristics were compared using conservative statistical thresholds (P < 0.01). All laboratory parameters were interpreted using age-adjusted pediatric reference ranges.

Among 53 patients (56.6% male), 43 had pulmonary abnormalities on HRCT. Common clinical features included skin lesions (43.4%), failure to thrive (34%), and autoimmunity (32.1%). HRCT revealed pneumonia (28.3%), bronchiectasis (18.9%), interstitial lung disease with BOOP-like pattern (3.8%), and other findings. Using age-adjusted pediatric reference ranges, profound immunological defects were confirmed: absolute lymphocyte count below the 5th percentile in 92% (49/53), CD3 + T cells below the 5th percentile in 94% (47/50 tested), CD4 + T cells below the 5th percentile in 96% (51/53), CD19 + B cells below the 5th percentile in 94% (50/53), and hypogammaglobulinaemia (IgG below the 5th percentile) in 98% (52/53). Patients with abnormal HRCT had significantly lower CD4 + T-cell counts (178 vs. 498 cells/µL; P = 0.008) and CD19 + B-cell counts (42 vs. 189 cells/µL; P = 0.009). Bronchoscopy identified Aspergillus fumigatus, Streptococcus pneumoniae, and multidrug-resistantAcinetobacter baumannii. Deceased patients showed significantly lower baseline platelets (183,000 vs. 266,000 cells/µL; P = 0.009), IgG (380 vs. 720 mg/dL; P = 0.007), and IgE (0.8 vs. 12 IU/mL; P = 0.008).

Pulmonary manifestations affect 81.1% of Iranian CID patients. Low baseline platelets, IgG, and IgE constitute a robust prognostic triad for mortality (P = 0.009, P = 0.007, P = 0.008 respectively). Application of age-adjusted reference ranges revealed profound immunological defects. Systematic HRCT surveillance using low-dose protocols and distinguishing infectious sequelae from immune-mediated lung disease guides targeted management in resource-limited settings.

The online version contains supplementary material available at 10.1186/s12890-026-04115-3.