Human inherited CCR2 deficiency underlies progressive polycystic lung disease

We describe a human lung disease caused by autosomal recessive, complete deficiency of the monocyte chemokine receptor C-C motif chemokine receptor 2 (CCR2). Nine children from five independent kindreds have pulmonary alveolar proteinosis (PAP), progressive polycystic lung disease, and recurrent infections, including bacillus Calmette Guérin (BCG) disease. The CCR2 variants are homozygous in six patients and compound heterozygous in three, and all are loss-of-expression and loss-of-function. They abolish CCR2-agonist chemokine C-C motif ligand 2 (CCL-2)-stimulated Ca(2+) signaling in and migration of monocytic cells. All patients have high blood CCL-2 levels, providing a diagnostic test for screening children with unexplained lung or mycobacterial disease. Blood myeloid and lymphoid subsets and interferon (IFN)-

• Neehus, A. L.
• Carey, B.
• Landekic, M.
• Panikulam, P.
• Deutsch, G.
• Ogishi, M.
• Arango-Franco, C. A.
• Philippot, Q.
• Modaresi, M.
• Mohammadzadeh, I.
• Corcini Berndt, M.
• Rinchai, D.
• Le Voyer, T.
• Rosain, J.
• Momenilandi, M.
• Martin-Fernandez, M.
• Khan, T.
• Bohlen, J.
• Han, J. E.
• Deslys, A.
• Bernard, M.
• Gajardo-Carrasco, T.
• Soudée, C.
• Le Floc'h, C.
• Migaud, M.
• Seeleuthner, Y.
• Jang, M. S.
• Nikolouli, E.
• Seyedpour, S.
• Begueret, H.
• Emile, J. F.
• Le Guen, P.
• Tavazzi, G.
• Colombo, C. N. J.
• Marzani, F. C.
• Angelini, M.
• Trespidi, F.
• Ghirardello, S.
• Alipour, N.
• Molitor, A.
• Carapito, R.
• Mazloomrezaei, M.
• Rokni-Zadeh, H.
• Changi-Ashtiani, M.
• Brouzes, C.
• Vargas, P.
• Borghesi, A.
• Lachmann, N.
• Bahram, S.
• Crestani, B.
• Pahari, S.
• Schlesinger, L. S.
• Marr, N.
• Bugonovic, D.
• Boisson-Dupuis, S.
• Béziat, V.
• Abel, L.
• Borie, R.
• Young, L. R.
• Deterding, R.
• Shahrooei, M.
• Rezaei, N.
• Parvaneh, N.
• Craven, D.
• Gros, P.
• Malo, D.
• Sepulveda, F. E.
• Nogee, L. M.
• Aladjidi, N.
• Trapnell, B. C.
• Casanova, J. L.
• Bustamante, J.