The Spectrum of Autoantibodies in Adult Patients With Idiopathic Pulmonary Hemosiderosis: A Brief Review of the Literature

Abstract

While autoimmune antibodies or autoantibodies have been reported sporadically in adult patients with idiopathic pulmonary hemosiderosis (IPH), their true prevalence is unknown. The question as to whether any difference exists between antibody-positive and negative patients has not been explored. The primary objective of this paper was to assess the spectrum of autoantibody testing and its positivity rate. The other objectives included a comparative analysis of demographics, symptom onset, clinical manifestations, and differences in clinical outcomes between antibody-positive (cohort A) and negative (cohort B) patients. To that end, we conducted a retrospective review of the relevant published literature. Multiple databases were searched to retrieve studies published between 1990 and 2022. A total of 35 studies, involving 38 patients, were identified. Five of these patients had a positive autoantibody. Patients in cohort A were older and more likely to be male. The frequencies of testing for these antibodies were as follows: antineutrophil cytoplasmic antibody (ANCA): 37/38 (97.4%), antinuclear antibody (ANA): 31/38 (81.6%), and anti-glomerular basement membrane antibody (anti-GBM): 30/38 (78.9%); 5/38 (13.2%) patients tested positive for an autoantibody, and two of these patients were positive for ANA, two for antithyroid antibody, and one patient tested positive for ANCA, rheumatoid factor (RF), and granulocyte monocyte-colony stimulating factor (GM-CSF) antibody. There was no difference between the cohorts regarding their clinical presentations, recurrence risks, and survival. The occurrence of autoantibodies is uncommon in adult IPH patients. This is in contrast with the pediatric IPH patient population, where the prevalence is much higher (26.4% vs. 13.2%), and the antibodies are more diverse. Unlike pediatric patients, adult patients with autoantibodies do not necessarily have worse outcomes.

Updates in idiopathic pulmonary hemosiderosis in 2022: A state of the art review

“…We believe that autoantibodies found in these patients may not be pathological (unlike in AAV) and either a bystander by coincidence or a manifestation of immunologic dysregulation in these patients but not necessarily involved in the DAH 29 . However, it is also possible that, at least in a minority of patients, IPH represents an attenuated form of AAV, which may eventually become evident after many years of follow‐up 24,25,45,67 . Interestingly, all adult patients with IPH for whom an ANCA has been reported to have developed demonstrated anti‐myeloperoxidase ANCA.…”

“…As DAH is a common presentation of AAV, an autoimmune workup is performed for nearly all patients suspected to have DAH. 97.8% of adult patients eventually diagnosed with IPH between 1990 and 2022 underwent testing for ANCA 45 . We have recently reported an overall prevalence of autoantibodies in both pediatric and adult patients with IPH.…”

“…There are some patients who have been diagnosed with IPH as a child but developed autoantibodies after a long period of time, ranging from 8 to 17 years 45 . The identification of these autoantibodies (ANCA and others) has fueled the autoimmune hypothesis in the causation of DAH in IPH patients for nearly 50 years 38,45 .…”

“…29 However, it is also possible that, at least in a minority of patients, IPH represents an attenuated form of AAV, which may eventually become evident after many years of follow-up. 24,25,45,67 Interestingly, all adult patients with IPH for whom an ANCA has been reported to have developed demonstrated anti-myeloperoxidase ANCA. Therefore, it could be possible that at and death in patients with LHS showed a lower trend than patients without CD (the difference did not reach statistical significance).…”

“…This high prevalence of anti‐CD antibodies was responsible for a relatively high rate of autoantibodies in adults, as stated above. If these patients were excluded, only five adult patients had non‐CD autoantibodies 45 . Two of these patients were positive for ANA, 2 for antithyroid antibody, and one patient each tested positive for ANCA, RF, and granulocyte monocyte‐colony stimulating factor antibody 24,63–66 .…”