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Autoimmune and Lymphoproliferative Complications of Common Variable Immunodeficiency

  • Paul J. MaglioneEmail author
Immune Deficiency and Dysregulation (DP Huston and C Kuo, Section Editors)
Part of the following topical collections:
  1. Topical Collection on Immune Deficiency and Dysregulation

Abstract

Common variable immunodeficiency (CVID) is frequently complicated by the development of autoimmune and lymphoproliferative diseases. With widespread use of immunoglobulin replacement therapy, autoimmune and lymphoproliferative complications have replaced infection as the major cause of morbidity and mortality in CVID patients. Certain CVID complications, such as bronchiectasis, are likely to be the result of immunodeficiency and are associated with infection susceptibility. However, other complications may result from immune dysregulation rather than immunocompromise. CVID patients develop autoimmunity, lymphoproliferation, and granulomas in association with distinct immunological abnormalities. Mutations in transmembrane activator and CAML interactor, reduction of isotype-switched memory B cells, expansion of CD21 low B cells, heightened interferon signature expression, and retained B cell function are all associated with both autoimmunity and lymphoproliferation in CVID. Further research aimed to better understand that the pathological mechanisms of these shared forms of immune dysregulation may inspire therapies beneficial for multiple CVID complications.

Keywords

Common variable immunodeficiency Autoimmunity Cytopenia Granulomatous disease Lymphoid hyperplasia 

Notes

Compliance with Ethical Standards

Conflict of Interest

Dr. Maglione declares no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    Cunningham-Rundles C, Maglione PJ. Common variable immunodeficiency. J Allergy Clin Immunol. 2012;129(5):1425–6. e3.CrossRefPubMedGoogle Scholar
  2. 2.
    Tseng CW, Lai KL, Chen DY, Lin CH, Chen HH. The incidence and prevalence of common variable immunodeficiency disease in Taiwan, a population-based study. PLoS One. 2015;10(10), e0140473.CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Chapel H, Cunningham-Rundles C. Update in understanding common variable immunodeficiency disorders (CVIDs) and the management of patients with these conditions. Br J Haematol. 2009;145(6):709–27.CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Ameratunga R, Brewerton M, Slade C, Jordan A, Gillis D, Steele R, et al. Comparison of diagnostic criteria for common variable immunodeficiency disorder. Front Immunol. 2014;5:415.CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Cunningham-Rundles C. The many faces of common variable immunodeficiency. Hematol Am Soc Hematol Educ Prog. 2012;2012:301–5.Google Scholar
  6. 6.••
    Chapel H, Lucas M, Lee M, Bjorkander J, Webster D, Grimbacher B, et al. Common variable immunodeficiency disorders: division into distinct clinical phenotypes. Blood. 2008;112(2):277–86. One of the earliest studies to divide CVID patients into divergent clinical phenotypes associated with distinct clinical and laboratory characteristics.CrossRefPubMedGoogle Scholar
  7. 7.
    Keller MD, Jyonouchi S. Chipping away at a mountain: genomic studies in common variable immunodeficiency. Autoimmun Rev. 2013;12(6):687–9.CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Lee JJ, Ozcan E, Rauter I, Geha RS. Transmembrane activator and calcium-modulator and cyclophilin ligand interactor mutations in common variable immunodeficiency. Curr Opin Allergy Clin Immunol. 2008;8(6):520–6.CrossRefPubMedGoogle Scholar
  9. 9.
    Hammarstrom L, Vorechovsky I, Webster D. Selective IgA deficiency (SIgAD) and common variable immunodeficiency (CVID). Clin Exp Immunol. 2000;120(2):225–31.CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Healy MJ. Hypogammaglobulinaemia in the United Kingdom. XII. Statistical analyses: prevalence, mortality and effects of treatment. Spec Rep Ser Med Res Counc (G B). 1971;310:115–23.Google Scholar
  11. 11.•
    Cunningham-Rundles C, Bodian C. Common variable immunodeficiency: clinical and immunological features of 248 patients. Clin Immunol. 1999;92(1):34–48. The first large study to report the clinical and immunological characteristics of CVID patients.CrossRefPubMedGoogle Scholar
  12. 12.
    Busse PJ, Razvi S, Cunningham-Rundles C. Efficacy of intravenous immunoglobulin in the prevention of pneumonia in patients with common variable immunodeficiency. J Allergy Clin Immunol. 2002;109(6):1001–4.CrossRefPubMedGoogle Scholar
  13. 13.
    Orange JS, Grossman WJ, Navickis RJ, Wilkes MM. Impact of trough IgG on pneumonia incidence in primary immunodeficiency: a meta-analysis of clinical studies. Clin Immunol. 2010;137(1):21–30.CrossRefPubMedGoogle Scholar
  14. 14.
    Jolles S. The variable in common variable immunodeficiency: a disease of complex phenotypes. J Allergy Clin Immunol Pract. 2013;1(6):545–56. Quiz 557.CrossRefPubMedGoogle Scholar
  15. 15.••
    Resnick ES, Moshier EL, Godbold JH, Cunningham-Rundles C. Morbidity and mortality in common variable immune deficiency over 4 decades. Blood. 2012;119(7):1650–7. Large longitudinal study at a single clinical center that identified divergent survival of CVID patients with or without inflammatory complications.CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.•
    Wehr C, Kivioja T, Schmitt C, Ferry B, Witte T, Eren E, et al. The EUROclass trial: defining subgroups in common variable immunodeficiency. Blood. 2008;111(1):77–85. This report highlighted the strong association between autoimmune cytopenias, splenomegaly, and granulomatous disease.CrossRefPubMedGoogle Scholar
  17. 17.•
    Gathmann B, Gathmann B, Mahlaoui N, Ceredih GL, Oksenhendler E, Warnatz K, et al. Clinical picture and treatment of 2212 patients with common variable immunodeficiency. J Allergy Clin Immunol. 2014;134(1):116–26. This is the largest report of clinical and laboratory features of CVID.CrossRefPubMedGoogle Scholar
  18. 18.
    Maglione PJ, Overbey JR, Radigan L, Bagiella E, Cunningham-Rundles C. Pulmonary radiologic findings in common variable immunodeficiency: clinical and immunological correlations. Ann Allergy Asthma Immunol. 2014;113(4):452–9.CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Quinti I, Soresina A, Guerra A, Rondelli R, Spadaro G, Agostini C, et al. Effectiveness of immunoglobulin replacement therapy on clinical outcome in patients with primary antibody deficiencies: results from a multicenter prospective cohort study. J Clin Immunol. 2011;31(3):315–22.CrossRefPubMedGoogle Scholar
  20. 20.
    Micol R, Kayal S, Mahlaoui N, Beaute J, Brosselin P, Dudoit Y, et al. Protective effect of IgM against colonization of the respiratory tract by nontypeable Haemophilus influenzae in patients with hypogammaglobulinemia. J Allergy Clin Immunol. 2012;129(3):770–7.CrossRefPubMedGoogle Scholar
  21. 21.
    Gregersen S, Holm AM, Fevang B, Ueland T, Sikkeland LI, Aalokken TM, et al. Lung disease, T-cells and inflammation in common variable immunodeficiency disorders. Scand J Clin Lab Invest. 2013;73(6):514–22.CrossRefPubMedGoogle Scholar
  22. 22.
    Boyton RJ, Reynolds CJ, Quigley KJ, Altmann DM. Immune mechanisms and the impact of the disrupted lung microbiome in chronic bacterial lung infection and bronchiectasis. Clin Exp Immunol. 2013;171(2):117–23.CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Daniels JA, Lederman HM, Maitra A, Montgomery EA. Gastrointestinal tract pathology in patients with common variable immunodeficiency (CVID): a clinicopathologic study and review. Am J Surg Pathol. 2007;31(12):1800–12.CrossRefPubMedGoogle Scholar
  24. 24.
    Malamut G, Verkarre V, Suarez F, Viallard JF, Lascaux AS, Cosnes J, et al. The enteropathy associated with common variable immunodeficiency: the delineated frontiers with celiac disease. Am J Gastroenterol. 2010;105(10):2262–75.CrossRefPubMedGoogle Scholar
  25. 25.
    Biagi F, Bianchi PI, Zilli A, Marchese A, Luinetti O, Lougaris V, et al. The significance of duodenal mucosal atrophy in patients with common variable immunodeficiency: a clinical and histopathologic study. Am J Clin Pathol. 2012;138(2):185–9.CrossRefPubMedGoogle Scholar
  26. 26.
    Zullo A, Romiti A, Rinaldi V, Vecchione A, Tomao S, Aiuti F, et al. Gastric pathology in patients with common variable immunodeficiency. Gut. 1999;45(1):77–81.CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    De Petris G, Dhungel BM, Chen L, Chang YH. Gastric adenocarcinoma in common variable immunodeficiency: features of cancer and associated gastritis may be characteristic of the condition. Int J Surg Pathol. 2014;22(7):600–6.CrossRefPubMedGoogle Scholar
  28. 28.
    Agarwal S, Mayer L. Diagnosis and treatment of gastrointestinal disorders in patients with primary immunodeficiency. Clin Gastroenterol Hepatol. 2013;11(9):1050–63.CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.•
    Gobert D, Bussel JB, Cunningham-Rundles C, Galicier L, Dechartres A, Berezne A, et al. Efficacy and safety of rituximab in common variable immunodeficiency-associated immune cytopenias: a retrospective multicentre study on 33 patients. Br J Haematol. 2011;155(4):498–508. This is an important retrospective study reporting the efficacy of rituximab in the treatment of autoimmune cytopenias in CVID.CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Boursiquot JN, Gerard L, Malphettes M, Fieschi C, Galicier L, Boutboul D, et al. Granulomatous disease in CVID: retrospective analysis of clinical characteristics and treatment efficacy in a cohort of 59 patients. J Clin Immunol. 2013;33(1):84–95.CrossRefPubMedGoogle Scholar
  31. 31.
    Hill F, Yonkof J, Chaitanya Arudra SK, Thomas J, Altorok N. Successful treatment of ANCA-associated vasculitis in the setting of common variable immunodeficiency using rituximab. Am J Ther. 2015.Google Scholar
  32. 32.
    Maglione PJ, Ko HM, Beasley MB, Strauchen JA, Cunningham-Rundles C. Tertiary lymphoid neogenesis is a component of pulmonary lymphoid hyperplasia in patients with common variable immunodeficiency. J Allergy Clin Immunol. 2014;133(2):535–42.CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Chase NM, Verbsky JW, Hintermeyer MK, Waukau JK, Tomita-Mitchell A, Casper JT, et al. Use of combination chemotherapy for treatment of granulomatous and lymphocytic interstitial lung disease (GLILD) in patients with common variable immunodeficiency (CVID). J Clin Immunol. 2013;33(1):30–9.CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Seidel MG. Autoimmune and other cytopenias in primary immunodeficiencies: pathomechanisms, novel differential diagnoses, and treatment. Blood. 2014;124(15):2337–44.CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Roskin KM, Simchoni N, Liu Y, Lee JY, Seo K, Hoh RA, et al. IgH sequences in common variable immune deficiency reveal altered B cell development and selection. Sci Transl Med. 2015;7(302), 302ra135.CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Daridon C, Loddenkemper C, Spieckermann S, Kuhl AA, Salama A, Burmester GR, et al. Splenic proliferative lymphoid nodules distinct from germinal centers are sites of autoantigen stimulation in immune thrombocytopenia. Blood. 2012;120(25):5021–31.CrossRefPubMedGoogle Scholar
  37. 37.
    Franchini M, Vescovi PP, Garofano M, Veneri D. Helicobacter pylori-associated idiopathic thrombocytopenic purpura: a narrative review. Semin Thromb Hemost. 2012;38(5):463–8.CrossRefPubMedGoogle Scholar
  38. 38.
    Rensing-Ehl A, Warnatz K, Fuchs S, Schlesier M, Salzer U, Draeger R, et al. Clinical and immunological overlap between autoimmune lymphoproliferative syndrome and common variable immunodeficiency. Clin Immunol. 2010;137(3):357–65.CrossRefPubMedGoogle Scholar
  39. 39.
    Kuehn HS, Ouyang W, Lo B, Deenick EK, Niemela JE, Avery DT, et al. Immune dysregulation in human subjects with heterozygous germline mutations in CTLA4. Science. 2014;345(6204):1623–7.CrossRefPubMedPubMedCentralGoogle Scholar
  40. 40.
    Schubert D, Bode C, Kenefeck R, Hou TZ, Wing JB, Kennedy A, et al. Autosomal dominant immune dysregulation syndrome in humans with CTLA4 mutations. Nat Med. 2014;20(12):1410–6.CrossRefPubMedPubMedCentralGoogle Scholar
  41. 41.
    Milner JD, Vogel TP, Forbes L, Ma CA, Stray-Pedersen A, Niemela JE, et al. Early-onset lymphoproliferation and autoimmunity caused by germline STAT3 gain-of-function mutations. Blood. 2015;125(4):591–9.CrossRefPubMedPubMedCentralGoogle Scholar
  42. 42.
    de Jager M, Blokx W, Warris A, Bergers M, Link M, Weemaes C, et al. Immunohistochemical features of cutaneous granulomas in primary immunodeficiency disorders: a comparison with cutaneous sarcoidosis. J Cutan Pathol. 2008;35(5):467–72.CrossRefPubMedGoogle Scholar
  43. 43.
    Tian X, Yi ES, Ryu JH. Lymphocytic interstitial pneumonia and other benign lymphoid disorders. Semin Respir Crit Care Med. 2012;33(5):450–61.CrossRefPubMedGoogle Scholar
  44. 44.
    Unger S, Seidl M, Schmitt-Graeff A, Bohm J, Schrenk K, Wehr C, et al. Ill-defined germinal centers and severely reduced plasma cells are histological hallmarks of lymphadenopathy in patients with common variable immunodeficiency. J Clin Immunol. 2014;34(6):615–26.CrossRefPubMedGoogle Scholar
  45. 45.
    Reddy DL, Venter WD, Pather S. Patterns of lymph node pathology; fine needle aspiration biopsy as an evaluation tool for lymphadenopathy: a retrospective descriptive study conducted at the largest hospital in Africa. PLoS One. 2015;10(6), e0130148.CrossRefPubMedPubMedCentralGoogle Scholar
  46. 46.
    Ko HM, da Cunha Santos G, Darling G, Pierre A, Yasufuku K, Boerner SL, et al. Diagnosis and subclassification of lymphomas and non-neoplastic lesions involving mediastinal lymph nodes using endobronchial ultrasound-guided transbronchial needle aspiration. Diagn Cytopathol. 2013;41(12):1023–30.CrossRefPubMedGoogle Scholar
  47. 47.
    Mellemkjaer L, Hammarstrom L, Andersen V, Yuen J, Heilmann C, Barington T, et al. Cancer risk among patients with IgA deficiency or common variable immunodeficiency and their relatives: a combined Danish and Swedish study. Clin Exp Immunol. 2002;130(3):495–500.CrossRefPubMedPubMedCentralGoogle Scholar
  48. 48.
    Piquer Gibert M, Alsina L, Giner Munoz MT, Cruz Martinez O, Ruiz Echevarria K, Dominguez O, et al. Non-Hodgkin lymphoma in pediatric patients with common variable immunodeficiency. Eur J Pediatr. 2015;174(8):1069–76.CrossRefPubMedGoogle Scholar
  49. 49.
    Zhang L, Radigan L, Salzer U, Behrens TW, Grimbacher B, Diaz G, et al. Transmembrane activator and calcium-modulating cyclophilin ligand interactor mutations in common variable immunodeficiency: clinical and immunologic outcomes in heterozygotes. J Allergy Clin Immunol. 2007;120(5):1178–85.CrossRefPubMedPubMedCentralGoogle Scholar
  50. 50.
    Romberg N, Chamberlain N, Saadoun D, Gentile M, Kinnunen T, Ng YS, et al. CVID-associated TACI mutations affect autoreactive B cell selection and activation. J Clin Invest. 2013;123(10):4283–93.CrossRefPubMedPubMedCentralGoogle Scholar
  51. 51.
    Xiao X, Miao Q, Chang C, Gershwin ME, Ma X. Common variable immunodeficiency and autoimmunity—an inconvenient truth. Autoimmun Rev. 2014;13(8):858–64.CrossRefPubMedGoogle Scholar
  52. 52.•
    Salzer U, Chapel HM, Webster AD, Pan-Hammarstrom Q, Schmitt-Graeff A, Schlesier M, et al. Mutations in TNFRSF13B encoding TACI are associated with common variable immunodeficiency in humans. Nat Genet. 2005;37(8):820–8. This report linked mutations in TACI with the development of CVID with high association with autoimmune and lymphoproliferative complications.CrossRefPubMedGoogle Scholar
  53. 53.
    Warnatz K, Wehr C, Drager R, Schmidt S, Eibel H, Schlesier M, et al. Expansion of CD19(hi)CD21(lo/neg) B cells in common variable immunodeficiency (CVID) patients with autoimmune cytopenia. Immunobiology. 2002;206(5):502–13.CrossRefPubMedGoogle Scholar
  54. 54.
    Abolhassani H, Amirkashani D, Parvaneh N, Mohammadinejad P, Gharib B, Shahinpour S, et al. Autoimmune phenotype in patients with common variable immunodeficiency. J Investig Allergol Clin Immunol. 2013;23(5):323–9.PubMedGoogle Scholar
  55. 55.
    Sanchez-Ramon S, Radigan L, Yu JE, Bard S, Cunningham-Rundles C. Memory B cells in common variable immunodeficiency: clinical associations and sex differences. Clin Immunol. 2008;128(3):314–21.CrossRefPubMedPubMedCentralGoogle Scholar
  56. 56.
    Isnardi I, Ng YS, Menard L, Meyers G, Saadoun D, Srdanovic I, et al. Complement receptor 2/CD21 human naive B cells contain mostly autoreactive unresponsive clones. Blood. 2010;115(24):5026–36.CrossRefPubMedPubMedCentralGoogle Scholar
  57. 57.
    Moir S, Ho J, Malaspina A, Wang W, DiPoto AC, O’Shea MA, et al. Evidence for HIV-associated B cell exhaustion in a dysfunctional memory B cell compartment in HIV-infected viremic individuals. J Exp Med. 2008;205(8):1797–805.CrossRefPubMedPubMedCentralGoogle Scholar
  58. 58.
    Terrier B, Joly F, Vazquez T, Benech P, Rosenzwajg M, Carpentier W, et al. Expansion of functionally anergic CD21−/low marginal zone-like B cell clones in hepatitis C virus infection-related autoimmunity. J Immunol. 2011;187(12):6550–63.CrossRefPubMedGoogle Scholar
  59. 59.
    Oraei M, Aghamohammadi A, Rezaei N, Bidad K, Gheflati Z, Amirkhani A, et al. Naive CD4+ T cells and recent thymic emigrants in common variable immunodeficiency. J Investig Allergol Clin Immunol. 2012;22(3):160–7.PubMedGoogle Scholar
  60. 60.
    Carter CR, Aravind G, Smalle NL, Cole JY, Savic S, Wood PM. CVID patients with autoimmunity have elevated T cell expression of granzyme B and HLA-DR and reduced levels of Treg cells. J Clin Pathol. 2013;66(2):146–50.CrossRefPubMedGoogle Scholar
  61. 61.
    Arandi N, Mirshafiey A, Jeddi-Tehrani M, Abolhassani H, Sadeghi B, Mirminachi B, et al. Evaluation of CD4+CD25+FOXP3+ regulatory T cells function in patients with common variable immunodeficiency. Cell Immunol. 2013;281(2):129–33.CrossRefPubMedGoogle Scholar
  62. 62.
    Arandi N, Mirshafiey A, Abolhassani H, Jeddi-Tehrani M, Edalat R, Sadeghi B, et al. Frequency and expression of inhibitory markers of CD4(+) CD25(+) FOXP3(+) regulatory T cells in patients with common variable immunodeficiency. Scand J Immunol. 2013;77(5):405–12.CrossRefPubMedGoogle Scholar
  63. 63.
    Genre J, Errante PR, Kokron CM, Toledo-Barros M, Camara NO, Rizzo LV. Reduced frequency of CD4(+)CD25(HIGH)FOXP3(+) cells and diminished FOXP3 expression in patients with common variable immunodeficiency: a link to autoimmunity? Clin Immunol. 2009;132(2):215–21.CrossRefPubMedGoogle Scholar
  64. 64.
    Knight AK, Radigan L, Marron T, Langs A, Zhang L, Cunningham-Rundles C. High serum levels of BAFF, APRIL, and TACI in common variable immunodeficiency. Clin Immunol. 2007;124(2):182–9.CrossRefPubMedPubMedCentralGoogle Scholar
  65. 65.
    Park J, Munagala I, Xu H, Blankenship D, Maffucci P, Chaussabel D, et al. Interferon signature in the blood in inflammatory common variable immune deficiency. PLoS One. 2013;8(9), e74893.CrossRefPubMedPubMedCentralGoogle Scholar
  66. 66.
    Cols M, Rahman A, Maglione PJ, Garcia-Carmona Y, Simchoni N, Ko HM, et al. Expansion of inflammatory innate lymphoid cells in patients with common variable immune deficiency. J Allergy Clin Immunol. 2015.Google Scholar
  67. 67.
    Wang J, Cunningham-Rundles C. Treatment and outcome of autoimmune hematologic disease in common variable immunodeficiency (CVID). J Autoimmun. 2005;25(1):57–62.CrossRefPubMedGoogle Scholar
  68. 68.
    Michel M, Chanet V, Galicier L, Ruivard M, Levy Y, Hermine O, et al. Autoimmune thrombocytopenic purpura and common variable immunodeficiency: analysis of 21 cases and review of the literature. Medicine (Baltimore). 2004;83(4):254–63.CrossRefGoogle Scholar
  69. 69.
    Wong GK, Goldacker S, Winterhalter C, Grimbacher B, Chapel H, Lucas M, et al. Outcomes of splenectomy in patients with common variable immunodeficiency (CVID): a survey of 45 patients. Clin Exp Immunol. 2013;172(1):63–72.CrossRefPubMedPubMedCentralGoogle Scholar
  70. 70.
    Quinti I, Soresina A, Spadaro G, Martino S, Donnanno S, Agostini C, et al. Long-term follow-up and outcome of a large cohort of patients with common variable immunodeficiency. J Clin Immunol. 2007;27(3):308–16.CrossRefPubMedGoogle Scholar
  71. 71.
    Sander CA, Medeiros LJ, Weiss LM, Yano T, Sneller MC, Jaffe ES. Lymphoproliferative lesions in patients with common variable immunodeficiency syndrome. Am J Surg Pathol. 1992;16(12):1170–82.CrossRefPubMedGoogle Scholar
  72. 72.
    Wheat WH, Cool CD, Morimoto Y, Rai PR, Kirkpatrick CH, Lindenbaum BA, et al. Possible role of human herpesvirus 8 in the lymphoproliferative disorders in common variable immunodeficiency. J Exp Med. 2005;202(4):479–84.CrossRefPubMedPubMedCentralGoogle Scholar
  73. 73.
    Andiman WA, Eastman R, Martin K, Katz BZ, Rubinstein A, Pitt J, et al. Opportunistic lymphoproliferations associated with Epstein-Barr viral DNA in infants and children with AIDS. Lancet. 1985;2(8469–70):1390–3.CrossRefPubMedGoogle Scholar
  74. 74.
    Barbera JA, Hayashi S, Hegele RG, Hogg JC. Detection of Epstein-Barr virus in lymphocytic interstitial pneumonia by in situ hybridization. Am Rev Respir Dis. 1992;145(4 Pt 1):940–6.CrossRefPubMedGoogle Scholar
  75. 75.
    San-Juan R, Comoli P, Caillard S, Moulin B, Hirsch HH, Meylan P, et al. Epstein-Barr virus-related post-transplant lymphoproliferative disorder in solid organ transplant recipients. Clin Microbiol Infect. 2014;20 Suppl 7:109–18.CrossRefPubMedGoogle Scholar
  76. 76.
    Castigli E, Wilson SA, Garibyan L, Rachid R, Bonilla F, Schneider L, et al. TACI is mutant in common variable immunodeficiency and IgA deficiency. Nat Genet. 2005;37(8):829–34.CrossRefPubMedGoogle Scholar
  77. 77.
    Maglione PJ, Overbey JR, Cunningham-Rundles C. Progression of common variable immunodeficiency interstitial lung disease accompanies distinct pulmonary and laboratory findings. J Allergy Clin Immunol Pract. 2015;3(6):941–50.CrossRefPubMedGoogle Scholar
  78. 78.
    Rao N, Mackinnon AC, Routes JM. Granulomatous and lymphocytic interstitial lung disease: a spectrum of pulmonary histopathologic lesions in common variable immunodeficiency—histologic and immunohistochemical analyses of 16 cases. Hum Pathol. 2015;46(9):1306–14.CrossRefPubMedGoogle Scholar
  79. 79.
    Bates CA, Ellison MC, Lynch DA, Cool CD, Brown KK, Routes JM. Granulomatous-lymphocytic lung disease shortens survival in common variable immunodeficiency. J Allergy Clin Immunol. 2004;114(2):415–21.CrossRefPubMedGoogle Scholar
  80. 80.
    Torigian DA, LaRosa DF, Levinson AI, Litzky LA, Miller Jr WT. Granulomatous-lymphocytic interstitial lung disease associated with common variable immunodeficiency: CT findings. J Thorac Imaging. 2008;23(3):162–9.CrossRefPubMedGoogle Scholar
  81. 81.
    Bondioni MP, Soresina A, Lougaris V, Gatta D, Plebani A, Maroldi R. Common variable immunodeficiency: computed tomography evaluation of bronchopulmonary changes including nodular lesions in 40 patients. Correlation with clinical and immunological data. J Comput Assist Tomogr. 2010;34(3):395–401.CrossRefPubMedGoogle Scholar
  82. 82.
    Carrillo J, Restrepo CS, Rosado de Christenson M, Ojeda Leon P, Lucia Rivera A, Koss MN. Lymphoproliferative lung disorders: a radiologic-pathologic overview. Part I: reactive disorders. Semin Ultrasound CT MR. 2013;34(6):525–34.CrossRefPubMedGoogle Scholar
  83. 83.
    Touw CM, van de Ven AA, de Jong PA, Terheggen-Lagro S, Beek E, Sanders EA, et al. Detection of pulmonary complications in common variable immunodeficiency. Pediatr Allergy Immunol. 2010;21(5):793–805.CrossRefPubMedGoogle Scholar
  84. 84.
    Kainulainen L, Varpula M, Liippo K, Svedstrom E, Nikoskelainen J, Ruuskanen O. Pulmonary abnormalities in patients with primary hypogammaglobulinemia. J Allergy Clin Immunol. 1999;104(5):1031–6.CrossRefPubMedGoogle Scholar
  85. 85.
    Fajgenbaum DC, van Rhee F, Nabel CS. HHV-8-negative, idiopathic multicentric Castleman disease: novel insights into biology, pathogenesis, and therapy. Blood. 2014;123(19):2924–33.CrossRefPubMedGoogle Scholar
  86. 86.
    Chiu CY. Viral pathogen discovery. Curr Opin Microbiol. 2013;16(4):468–78.CrossRefPubMedGoogle Scholar
  87. 87.
    Carson KR, Evens AM, Richey EA, Habermann TM, Focosi D, Seymour JF, et al. Progressive multifocal leukoencephalopathy after rituximab therapy in HIV-negative patients: a report of 57 cases from the research on adverse drug events and reports project. Blood. 2009;113(20):4834–40.CrossRefPubMedPubMedCentralGoogle Scholar
  88. 88.
    Chien SH, Liu CJ, Hong YC, Teng CJ, Hu YW, Shen CC, et al. Use of azathioprine for graft-vs-host disease is the major risk for development of secondary malignancies after haematopoietic stem cell transplantation: a nationwide population-based study. Br J Cancer. 2015;112(1):177–84.CrossRefPubMedPubMedCentralGoogle Scholar
  89. 89.
    Ardeniz O, Cunningham-Rundles C. Granulomatous disease in common variable immunodeficiency. Clin Immunol. 2009;133(2):198–207.CrossRefPubMedPubMedCentralGoogle Scholar
  90. 90.
    Yong PF, Thaventhiran JE, Grimbacher B. “A rose is a rose is a rose,” but CVID is not CVID common variable immune deficiency (CVID), what do we know in 2011? Adv Immunol. 2011;111:47–107.CrossRefPubMedGoogle Scholar
  91. 91.
    Davies CW, Juniper MC, Gray W, Gleeson FV, Chapel HM, Davies RJ. Lymphoid interstitial pneumonitis associated with common variable hypogammaglobulinaemia treated with cyclosporin A. Thorax. 2000;55(1):88–90.CrossRefPubMedPubMedCentralGoogle Scholar
  92. 92.
    Kohler PF, Cook RD, Brown WR, Manguso RL. Common variable hypogammaglobulinemia with T-cell nodular lymphoid interstitial pneumonitis and B-cell nodular lymphoid hyperplasia: different lymphocyte populations with a similar response to prednisone therapy. J Allergy Clin Immunol. 1982;70(4):299–305.CrossRefPubMedGoogle Scholar
  93. 93.
    Malbran A, Juri MC, Fernandez Romero DS. Common variable immunodeficiency and granulomatosis treated with infliximab. Clin Immunol. 2010;134(3):359–60.CrossRefPubMedGoogle Scholar
  94. 94.
    Franxman TJ, Howe LE, Baker Jr JR. Infliximab for treatment of granulomatous disease in patients with common variable immunodeficiency. J Clin Immunol. 2014;34(7):820–7.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  1. 1.Division of Clinical Immunology, Department of MedicineIcahn School of Medicine at Mount SinaiNew YorkUSA

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