Pulmonary Langerhans Cell Histiocytosis—Insight into the Incidence of Alfa-1-Antitrypsin Deficiency (A1ATD) Alleles

Abstract

Introduction: The alpha-1 antitrypsin deficiency (A1ATD) is one of the three most common genetic disorders in Caucasians. It considerably increases the risk of progressive obstructive lung diseases, mostly chronic obstructive pulmonary disease. There is no data regarding the prevalence of main, clinically most important A1ATD alleles PI*Z and PI*S in patients with pulmonary Langerhans cell histiocytosis (PLCH). PLCH is not only strongly linked to the cigarette smoking, but is also characterised by polycystic lung lesions. The goal of the study was to assess the incidence of A1ATD alleles in patients with PLCH. Material and methods: Blood samples were collected from 34 adult patients (14 women and 20 men), with histologically confirmed PLCH. AAT serum concentration was assessed by nephelometry and PI-phenotype, identified by isoelectrofocusing. The PI*S and PI*Z alleles were confirmed by genotyping using real-time PCR. Results: Deficiency alleles PI*Z and PI*S were detected in 3 patients (one woman and 2 men), in 5.88% and 2.94% respectively. The estimated incidence of deficiency alleles was 29.4/1000 (95% CI; 10-69.5) for PI*Z and 14.7/1000(95%CI; 13.9-43.3) for PI*S. According to our previous reports, the expected prevalence of PI*Z and PI*S alleles in the general Polish population was 13.7/1000 (95% CI 5.8-21.5), and 7,6/1000 (95% CI 1.7-13.5) respectively. Conclusions: The incidence of main A1AT deficiency alleles in patients with PLCH seems higher than in the general Polish population. The study is ongoing.

Clarifying the relationship between pulmonary langerhans cell histiocytosis and Alpha 1 antitrypsin deficiency

“…Consequently, it has been hypothesized that there may be a link between PLCH and AATD through a common pathway of proteolytic damage, further augmented by smoking [13]. In a small study conducted on 34 patients with PLCH there was an increased frequency of deficient AATD alleles noted, PiZ and PiS accounting for 5.88% and 2.94% of alleles [14]. To further clarify this proposed relationship, we sought to measure AAT levels and evaluate AAT phenotype in a large series of carefully classified PLCH patients, including both predominant diffuse cystic lung disease pattern and the nodulo-cystic pattern of PLCH.…”

Update on α1-antitrypsin deficiency

“…Signs and symptoms of pulmonary involvement with AATD closely resemble those of other patients with COPD. However, a very recent study on 500 severe AATD subjects has provided evidence that nearly 46% of all participants were diagnosed with either asthma or allergic disease [ 20 ], and a higher incidence of the main AATD alleles has recently been detected in pulmonary Langerhans cell histiocytosis [ 21 ].…”