nach oben

Erschienen in:

01.08.2014 | Original Research

Ill-Defined Germinal Centers and Severely Reduced Plasma Cells are Histological Hallmarks of Lymphadenopathy in Patients with Common Variable Immunodeficiency

verfasst von: Susanne Unger, Maximilian Seidl, Annette Schmitt-Graeff, Joachim Böhm, Klaudia Schrenk, Claudia Wehr, Sigune Goldacker, Ruth Dräger, Barbara C. Gärtner, Paul Fisch, Martin Werner, Klaus Warnatz

Erschienen in: Journal of Clinical Immunology | Ausgabe 6/2014

Einloggen, um Zugang zu erhalten

Abstract

Given the severely reduced numbers of circulating class-switched memory B cells and plasmablasts in patients with common variable immunodeficiency (CVID) the germinal center (GC) reaction as the source of both populations is expected to be disturbed in many CVID patients. Therefore immunohistochemical studies were performed on lymph node (LN) biopsies from ten CVID patients with benign lymphoproliferation. According to the Sander classification the majority of patients presented with reactive lymphoid hyperplasia (7/10), 6/10 showed granulomatous inflammation. All cases showed some normal GCs but in 9/10 these concurred to a varying degree with hyperplastic, ill-defined GCs in the same LN. The percentage of ill-defined GCs correlated significantly with the percentage of circulating CD21^low B cells suggesting a common origin of both immune reactions. In 9/10 CVID LNs significantly higher numbers of infiltrating CD8⁺ T cells were found in GCs of CVID patients compared to controls, but no HHV-8 and only in 2/10 LNs EBV infection was detected. Class switched plasma cells (PCs) were severely reduced in 8/10 LNs and if present, rarely found in the medulla of the LN. Based on the presence of large GCs in all examined patients, the reduction of circulating memory B cells and PCs points towards a failure of GC output rather than GC formation in CVID patients with lymphadenopathy.

Nur mit Berechtigung zugänglich

Warnatz K, Denz A, Drager R, Braun M, Groth C, Wolff-Vorbeck G, et al. Severe deficiency of switched memory B cells (CD27(+)IgM(−)IgD(−)) in subgroups of patients with common variable immunodeficiency: a new approach to classify a heterogeneous disease. Blood. 2002;99(5):1544–51.PubMedCrossRef

DiSanto JP, Bonnefoy JY, Gauchat JF, Fischer A, de Saint BG. CD40 ligand mutations in x-linked immunodeficiency with hyper-IgM. Nature. 1993;361(6412):541–3.PubMedCrossRef

Ferrari S, Giliani S, Insalaco A, Al-Ghonaium A, Soresina AR, Loubser M, et al. Mutations of CD40 gene cause an autosomal recessive form of immunodeficiency with hyper IgM. Proc Natl Acad Sci U S A. 2001;98(22):12614–9.PubMedCentralPubMedCrossRef

Warnatz K, Bossaller L, Salzer U, Skrabl-Baumgartner A, Schwinger W, van der Burg M, et al. Human ICOS deficiency abrogates the germinal center reaction and provides a monogenic model for common variable immunodeficiency. Blood. 2006;107(8):3045–52.PubMedCrossRef

Qi H, Cannons JL, Klauschen F, Schwartzberg PL, Germain RN. SAP-controlled T-B cell interactions underlie germinal centre formation. Nature. 2008;455(7214):764–9.PubMedCentralPubMedCrossRef

Revy P, Muto T, Levy Y, Geissmann F, Plebani A, Sanal O, et al. Activation-induced cytidine deaminase (AID) deficiency causes the autosomal recessive form of the Hyper-IgM syndrome (HIGM2). Cell. 2000;102(5):565–75.PubMedCrossRef

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.PubMedCrossRef

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.PubMedCrossRef

Groth C, Drager R, Warnatz K, Wolff-Vorbeck G, Schmidt S, Eibel H, et al. Impaired up-regulation of CD70 and CD86 in naive (CD27-) B cells from patients with common variable immunodeficiency (CVID). Clin Exp Immunol. 2002;129(1):133–9.PubMedCentralPubMedCrossRef

10.

Fischer MB, Hauber I, Eggenbauer H, Thon V, Vogel E, Schaffer E, et al. A defect in the early phase of T-cell receptor-mediated T-cell activation in patients with common variable immunodeficiency. Blood. 1994;84(12):4234–41.PubMed

11.

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.PubMedCentralPubMedCrossRef

12.

Conley ME, Notarangelo LD, Etzioni A. Diagnostic criteria for primary immunodeficiencies. Representing PAGID (Pan-American Group for Immunodeficiency) and ESID (European Society for Immunodeficiencies). Clin Immunol. 1999;93(3):190–7.PubMedCrossRef

13.

Kojima M, Nakamura S, Itoh H, Motoori T, Sugihara S, Shinkai H, et al. Angioimmunoblastic T-cell lymphoma with hyperplastic germinal centers: a clinicopathological and immunohistochemical study of 10 cases. APMIS. 2001;109(10):699–706.PubMedCrossRef

14.

Toccanier MF, Kapanci Y. Lymphadenopathy in drug addicts. A study of the distribution of T lymphocyte subsets in the lymph nodes. Virchows Archiv A, Pathological Anat Histopathol. 1985;406(2):149–63.CrossRef

15.

O’Malley DPGT, Orazi A, Abbondanzo SL. General Reactive Conditions in Lymph Node and Spleen. In: O’Malley DPGT, Orazi A, Abbondanzo SL, editors. Atlas of Nontumor Pathology 7 Benign & Reactive Conditions Lymph Node & Spleen. 1st ed. Washington, DC: The American Registry of Pathology; 2009. p. 129–33.

16.

Chan PK, Ng HK, Cheung JL, Cheng AF. Survey for the presence and distribution of human herpesvirus 8 in healthy brain. J Clin Microbiol. 2000;38(7):2772–3.PubMedCentralPubMed

17.

Warnatz K, Schlesier M. Flowcytometric phenotyping of common variable immunodeficiency. Cytometry B Clin Cytom. 2008;74(5):261–71.PubMedCrossRef

18.

Chevalier N, Jarrossay D, Ho E, Avery DT, Ma CS, Yu D, et al. CXCR5 expressing human central memory CD4 T cells and their relevance for humoral immune responses. J Immunol. 2011;186(10):5556–68.PubMedCrossRef

19.

Morita R, Schmitt N, Bentebibel SE, Ranganathan R, Bourdery L, Zurawski G, et al. Human blood CXCR5(+)CD4(+) T cells are counterparts of T follicular cells and contain specific subsets that differentially support antibody secretion. Immunity. 2011;34(1):108–21.PubMedCentralPubMedCrossRef

20.

Ochtrop ML, Goldacker S, May AM, Rizzi M, Draeger R, Hauschke D, et al. T and B lymphocyte abnormalities in bone marrow biopsies of common variable immunodeficiency. Blood. 2011;118(2):309–18.PubMedCrossRef

21.

Taubenheim N, von Hornung M, Durandy A, Warnatz K, Corcoran L, Peter HH, et al. Defined blocks in terminal plasma cell differentiation of common variable immunodeficiency patients. J Immunol. 2005;175(8):5498–503.PubMedCrossRef

22.

Herbst EW, Armbruster M, Rump JA, Buscher HP, Peter HH. Intestinal B cell defects in common variable immunodeficiency. Clin Exp Immunol. 1994;95(2):215–21.PubMedCentralPubMedCrossRef

23.

Scott LJ, Bryant A, Webster AD, Farrant J. Failure in IgA secretion by surface IgA-positive B cells in common variable immunodeficiency (CVID). Clin Exp Immunol. 1994;95(1):10–3.PubMedCentralPubMedCrossRef

24.

Fossum S, Ford WL. The organization of cell populations within lymph nodes: their origin, life history and functional relationships. Histopathology. 1985;9(5):469–99.PubMedCrossRef

25.

van der Valk P MC. The Lymph Nodes. In: Mills SE, editors. Histology for Pathologists. 3 ed. Philadelphia: Lippincott Williams and Wilkins; 2007. pp. 763–81.

26.

Humpert ML, Pinto D, Jarrossay D, Thelen M. CXCR7 influences the migration of B cells during maturation. European journal of immunology. 2013.

27.

Kojima M, Kashimura M, Itoh H, Noro M, Matsuda H, Tsukamoto N. Infectious mononucleosis lymphoadenitis showing histologic findings indistinguishable from toxoplasma lymphadenitis. A report of three cases. Pathol Res Pract. 2010;206(6):361–4.PubMedCrossRef

28.

Gujral S, Gandhi JS, Valsangkar S, Shet TM, Epari S, Subramanian PG. Study of the morphological patterns and association of Epstein-Barr virus and human herpes virus 8 in acquired immunodeficiency deficiency syndrome-related reactive lymphadenopathy. Indian J Pathol Microbiol. 2010;53(4):723–8.PubMedCrossRef

29.

Turner RR, Levine AM, Gill PS, Parker JW, Meyer PR. Progressive histopathologic abnormalities in the persistent generalized lymphadenopathy syndrome. Am J Surg Pathol. 1987;11(8):625–32.PubMedCrossRef

30.

Kojima M, Kitamoto Y, Shimizu K, Matsuda H, Masawa N. Tonsillar lesions of infectious mononucleosis resembling MALT type lymphoma. A report of two cases. Pathol Oncol Res: POR. 2008;14(4):489–92.PubMedCrossRef

31.

Mrusek S, Marx A, Kummerle-Deschner J, Tzaribachev N, Enders A, Riede UN, et al. Development of granulomatous common variable immunodeficiency subsequent to infection with Toxoplasma gondii. Clin Exp Immunol. 2004;137(3):578–83.PubMedCentralPubMedCrossRef

32.

Siim JC, Nissen NI. Toxoplasmosis acquisita lymphonodosa in a 62-year-old woman; isolation of Toxoplasma gondli from lymph node and muscle biopsies. Acta Pathol Microbiol Scand. 1958;43(3):298–304.PubMedCrossRef

33.

Sheibani K, Fritz RM, Winberg CD, Burke JS, Rappaport H. “Monocytoid” cells in reactive follicular hyperplasia with and without multifocal histiocytic reactions: an immunohistochemical study of 21 cases including suspected cases of toxoplasmic lymphadenitis. Am J Clin Pathol. 1984;81(4):453–8.PubMed

34.

Dargent JL, Haller A, Durdurez JP, Gennotte AF. Atypical hyperplasia of the marginal zone of B follicles in a polymorphic Epstein-Barr virus-associated lymphoproliferative disorder occurring in an adolescent with human immunodeficiency virus infection. Pediatr Dev Pathol: the official journal of the Society for Pediatric Pathology and the Paediatric Pathology Society. 2009;12(1):59–62.CrossRef

35.

Ree HJ, Kadin ME, Kikuchi M, Ko YH, Go JH, Suzumiya J, et al. Angioimmunoblastic lymphoma (AILD-type T-cell lymphoma) with hyperplastic germinal centers. Am J Surg Pathol. 1998;22(6):643–55.PubMedCrossRef

36.

Ree HJ, Kadin ME, Kikuchi M, Ko YH, Suzumiya J, Go JH. Bcl-6 expression in reactive follicular hyperplasia, follicular lymphoma, and angioimmunoblastic T-cell lymphoma with hyperplastic germinal centers: heterogeneity of intrafollicular T-cells and their altered distribution in the pathogenesis of angioimmunoblastic T-cell lymphoma. Hum Pathol. 1999;30(4):403–11.PubMedCrossRef

37.

Dezube BJ, Aboulafia DM, Pantanowitz L. Plasma cell disorders in HIV-infected patients: from benign gammopathy to multiple myeloma. AIDS Read. 2004;14(7):372–4. 7–9.PubMed

38.

O’Murchadha MT, Wolf BC, Neiman RS. The histologic features of hyperplastic lymphadenopathy in AIDS-related complex are nonspecific. Am J Surg Pathol. 1987;11(2):94–9.PubMedCrossRef

39.

Zhang Y, Meyer-Hermann M, George LA, Figge MT, Khan M, Goodall M, et al. Germinal center B cells govern their own fate via antibody feedback. J Exp Med. 2013;210(3):457–64.PubMedCentralPubMedCrossRef

40.

Mouillot G, Carmagnat M, Gerard L, Garnier JL, Fieschi C, Vince N, et al. B-cell and T-cell phenotypes in CVID patients correlate with the clinical phenotype of the disease. J Clin Immunol. 2010;30(5):746–55.PubMedCrossRef

41.

Rakhmanov M, Keller B, Gutenberger S, Foerster C, Hoenig M, Driessen G, et al. Circulating CD21low B cells in common variable immunodeficiency resemble tissue homing, innate-like B cells. Proc Natl Acad Sci U S A. 2009;106(32):13451–6.PubMedCentralPubMedCrossRef

42.

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.PubMedCrossRef

43.

Al Kindi M, Mundy J, Sullivan T, Smith W, Kette F, Smith A, et al. Utility of peripheral blood B cell subsets analysis in common variable immunodeficiency. Clin Exp Immunol. 2012;167(2):275–81.PubMedCentralPubMedCrossRef

44.

Asano S. Granulomatous lymphadenitis. J Clin Exp Hematopathology : JCEH. 2012;52(1):1–16.CrossRef

45.

Kuntz M, Goldacker S, Blum HE, Pircher H, Stampf S, Peter HH, et al. Analysis of bulk and virus-specific CD8+ T cells reveals advanced differentiation of CD8+ T cells in patients with common variable immunodeficiency. Clin Immunol. 2011;141(2):177–86.PubMedCrossRef

46.

Kim HJ, Verbinnen B, Tang X, Lu L, Cantor H. Inhibition of follicular T-helper cells by CD8(+) regulatory T cells is essential for self tolerance. Nature. 2010;467(7313):328–32.PubMedCentralPubMedCrossRef

47.

Quigley MF, Gonzalez VD, Granath A, Andersson J, Sandberg JK. CXCR5+ CCR7–CD8 T cells are early effector memory cells that infiltrate tonsil B cell follicles. Eur J Immunol. 2007;37(12):3352–62.PubMedCrossRef

48.

Racz P, Tenner-Racz K, van Vloten F, Schmidt H, Dietrich M, Gluckman JC, et al. Lymphatic tissue changes in AIDS and other retrovirus infections: tools and insights. Lymphology. 1990;23(2):85–91.PubMed

49.

Keller AR, Hochholzer L, Castleman B. Hyaline-vascular and plasma-cell types of giant lymph node hyperplasia of the mediastinum and other locations. Cancer. 1972;29(3):670–83.PubMedCrossRef

50.

Schulte KM, Talat N. Castleman’s disease–a two compartment model of HHV8 infection. Nat Rev Clin Oncol. 2010;7(9):533–43.PubMedCrossRef

Titel: Ill-Defined Germinal Centers and Severely Reduced Plasma Cells are Histological Hallmarks of Lymphadenopathy in Patients with Common Variable Immunodeficiency
verfasst von: Susanne Unger
Maximilian Seidl
Annette Schmitt-Graeff
Joachim Böhm
Klaudia Schrenk
Claudia Wehr
Sigune Goldacker
Ruth Dräger
Barbara C. Gärtner
Paul Fisch
Martin Werner
Klaus Warnatz
Publikationsdatum: 01.08.2014
Verlag: Springer US
Erschienen in: Journal of Clinical Immunology / Ausgabe 6/2014
Print ISSN: 0271-9142
Elektronische ISSN: 1573-2592
DOI: https://doi.org/10.1007/s10875-014-0052-1

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

^{Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag}

Kostenlos registrieren

Neu im Fachgebiet Innere Medizin

„Jeder Fall von plötzlichem Tod muss obduziert werden!“

17.05.2024 Plötzlicher Herztod Nachrichten

Ein signifikanter Anteil der Fälle von plötzlichem Herztod ist genetisch bedingt. Um ihre Verwandten vor diesem Schicksal zu bewahren, sollten jüngere Personen, die plötzlich unerwartet versterben, ausnahmslos einer Autopsie unterzogen werden.

Hirnblutung unter DOAK und VKA ähnlich bedrohlich

17.05.2024 Direkte orale Antikoagulanzien Nachrichten

Kommt es zu einer nichttraumatischen Hirnblutung, spielt es keine große Rolle, ob die Betroffenen zuvor direkt wirksame orale Antikoagulanzien oder Marcumar bekommen haben: Die Prognose ist ähnlich schlecht.

Schlechtere Vorhofflimmern-Prognose bei kleinem linken Ventrikel

17.05.2024 Vorhofflimmern Nachrichten

Nicht nur ein vergrößerter, sondern auch ein kleiner linker Ventrikel ist bei Vorhofflimmern mit einer erhöhten Komplikationsrate assoziiert. Der Zusammenhang besteht nach Daten aus China unabhängig von anderen Risikofaktoren.

Semaglutid bei Herzinsuffizienz: Wie erklärt sich die Wirksamkeit?

17.05.2024 Herzinsuffizienz Nachrichten

Bei adipösen Patienten mit Herzinsuffizienz des HFpEF-Phänotyps ist Semaglutid von symptomatischem Nutzen. Resultiert dieser Benefit allein aus der Gewichtsreduktion oder auch aus spezifischen Effekten auf die Herzinsuffizienz-Pathogenese? Eine neue Analyse gibt Aufschluss.

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Die Highlights vom Kongress des American College of Cardiology 2024

Springer Medizin

Abstract

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 6/2014

Early Systemic Sclerosis: Serum Profiling of Factors Involved in Endothelial, T-cell, and Fibroblast Interplay is Marked by Elevated Interleukin-33 Levels

Autoimmunity and Inflammation in X-linked Agammaglobulinemia

High Level Antibody Avidity is Achieved in HIV-Seropositive Recipients of an Inactivated Split Adjuvanted (AS03A) Influenza Vaccine

Autologous Human Cytomegalovirus-Specific Cytotoxic T Cells as Rescue Therapy for Ulcerative Enteritis in Primary Immunodeficiency

A Complement Factor B Mutation in a Large Kindred with Atypical Hemolytic Uremic Syndrome