To describe a potential new non-neurologic manifestation of contactin-1 IgG associated autoimmune nodopathy (CNTN1 AN).

We report two cases of CNTN1 AN linked to inflammatory pulmonary disease. Airway epithelial cells exposed to allergens have been shown to release CNTN1-bearing exosomes, which activate dendritic cells and promote Th2/Th17 responses. Elevated CNTN1 levels have also been found in the serum and lung tissues of asthma patients compared to healthy controls.

Case series.

Case 1: A 63-year-old man was diagnosed with CNTN1 AN after presenting with a chronic sensory-predominant demyelinating polyradiculoneuropathy, neuropathic pain, dysautonomia, lambda monoclonal paraproteinemia, and lymphadenopathy, along with positive CNTN1 IgG. At the time of diagnosis, he developed acute respiratory failure due to obstructive airway disease. A CT chest showed ground-glass pulmonary opacities. He also had hypereosinophilia (absolute eosinophil count 1.31x10⁹/L, normal 0.03-0.48x10⁹/L) and elevated IgE levels (5530kU/L, normal ≤214kU/L), leading to a diagnosis of new-onset asthma.

Case 2: A 33-year-old man was diagnosed with CNTN1 AN and biopsy-proven membranous nephropathy after presenting with a chronic sensory-predominant demyelinating polyradiculoneuropathy, proteinuria, lymphadenopathy, and polyclonal gammopathy (IgM and IgG), with positive CNTN1 IgG. A CT chest revealed asymptomatic ground-glass and cystic pulmonary changes. Pulmonary function tests and eosinophil counts were normal, and IgE levels were not measured. A lung biopsy showed follicular bronchiolitis with chronic interstitial inflammation, leading to a diagnosis of interstitial pneumonitis.

Both patients had no prior history of pulmonary disease. Extensive investigations for chronic infections (e.g., HIV, HHV8), systemic autoimmune conditions, and lymphoproliferative disorders yielded negative results. Both were treated with steroids and rituximab, resulting in good clinical outcomes.

These cases highlight a potential link between CNTN1 autoimmunity and pulmonary involvement. Further research, including additional cases, is needed to confirm this association and clarify the role of CNTN1 IgG in inflammatory lung disease.