Conclusions
This study has provided information on the spectrum of changes which can occur in different PID. Using a pattern-based approach for the analysis of the lymph node parenchyma, it is obvious that there are no morphological features specifically associated with a single disease. This indicates that the lymph node biopsy is per se insufficient to identify any specific form of PID. There are, however, a few exceptions: with the advantage of immunohistochemistry we found severe abnormalities of FDC in X-linked hyper-IgM, which can be used for diagnostic purposes. Other morphological phenotypical features of lymph nodes, when correlated with clinical and hematological data, can be relevant for the correct attribution to a specific disease: a lymph node with preserved cellularity is never found in T−B− SCID, unless associated with engraftment of maternal/donor lymphocytes. On the other hand, lymph node changes that have been considered characteristic of OS, can also be observed in other conditions, and may sometimes derive from associated skin diseases. This indicates that the distinction between these PID might not be absolute, not only in terms of morphology, but also in terms of cell defects and pathogenesis.
The heterogeneity of lymph node histology observed within the same disease can be explained by the complex of interactions regulating the ontogeny and development of lymphoid organs. In addition, it may reflect the phenomenon of identical genetic anomalies that give different phenotypes [72]. In certain conditions, such as the WAS, this morphological variability can be correlated with clinical variations of the disease, and can be helpful in the study of the biological mechanisms associated with gene mutations and protein expression defects.
Knowledge of the spectrum of changes which can be found in lymph nodes in different forms of PID may be helpful not only in better defining the clinical diagnosis, but also in the evaluation of biopsy/autopsy material from patients who died without a precise diagnosis being made, and in genetic counselling. With the help of advanced techniques, such as in situ hybridization for mRNA encoding specific immune-related gene products, the study of lymph node biopsy samples will provide greater insight into the processes regulating the immune response, in normal and pathological conditions.
Similar content being viewed by others
References
Bahadoran P, Rieux-Laucat F, Canioni D, Le Diest F, Fischer A, Brousse N (1996) Significance of interdigitating reticulum cells in Omenn's syndrome. Am J Surg Pathol 20:1032
Bruton OC (1952) Agammaglobulinemia. Pediatrics 9:722
Buckley RH, Schiff RI, Schiff SE, Markett LM, Williams LW, Harville TO, Roberts JL, Puck JM (1997) Human severe combined immunodeficiency: genetic, phenotipic, and functional diversity in one hundred eight infants. J Pediatr 130:378
Businco L, Di Fazio A, Ziruolo MG, Boner AL, Valletta EA, Ruco LP, Vitolo D, Ensoli B, Paganelli R (1987) Clinical and immunological findings in four infants with Omenn's syndrome: a form of severe combined immunodeficiency with phenotypically normal T cells, elevated IgE, and eosinophilia. Clin Immunol Immunopathol 44:123
Cao X, Shores EW, Hu-Li J, Anver MR, Kelsall BL, Russel SM, Drago J, Noguchi M, Grinberg A, Bloom ET, Paul PE, Katz SI, Love PE, Leonard WJ (1995) Defective lymphoid development in mice lacking expression of the common cytokine receptor chain. Immunity 2:223
Castenholz A (1990) Architecture of the lymph node with regard to its function. In: Grundmann E, Vollmer E (eds) Reaction patterns of the lymph node. Part 1. Cell types and functions. Springer, Berlin Heidelberg New York, pp 1–32
Caux C, Vanbervliet B, Massacrier C, Dezutter-Dambuyant C, Saint-Vis B de, Jacquet C, Yoneda K, Imamura S, Schmitt D, Banchereau J (1996) CD34+ hematopoietic progenitors from human cord blood differentiate along two independent dendritic cell pathways in response to GM-CSF+TNFα. J Exp Med 184:695
Chilosi M, Facchetti F, Notarangelo LD, Romagnani S, Del Prete G, Almerigogna F, De Carli M, Pizzolo G (1996) CD30 cell expression and abnormal soluble CD30 serum accumulation in Omenn's syndrome: evidence for a T helper 2-mediated condition. Eur J Immunol 26:329
Conley ME (1985) B cells in patients with X-linked agammaglobulinemia. J Immunol 134:3070
Cottier H, Turk J, Sobin L (1973) A proposal for a standardized system of reporting human lymph node morphology in relation to immunological function. J Clin Pathol 26:317
Cottier H, Kraft R, Meister F (1990) Primary immunodeficiency syndromes and their manifestations in lymph nodes. In: Grundmann E, Vollmer E (eds) Reaction patterns of the lymph node. Part 2. Reactions associated with neoplasia and immune deficient states. Springer, Berlin Heidelberg New York, pp 81–155
De Bruyn PPH, Cho Y (1990) Structure and function of high endothelial postcapillary venules in lymphocyte circulation. In: Grundmann E, Vollmer E (eds) Reaction patterns of the lymph node. Part 1. Cell types and functions. Springer, Berlin Heidelberg New York, pp 85–101
Derry JMJ, Ochs HD, Francke U (1994) Isolation of a novel gene mutated in Wiskott-Aldrich syndrome. Cell 78: 635
De Saint-Basile G, Le Diest F, Villartay JP de, Cerf-Bemussan N, Joumet O, Brousse N, Griscelli C, Fischer A (1991) Restricted heterogeneity of T lymphocytes in combined immunodeficiency with hypereosinophilia (Omenn's syndrome). J Clin Invest 87:1352
De Wolf-Peeters C, Delabie J (1993) Anatomy and histopathology of lymphoid tissue. Semin Oncol 20:555
Donner M, Schwartz M, Carlsson KU, Holmberg L (1988) Hereditary X-linked thrombocytopenia maps to the same chromosomal region as the Wiskott-Aldrich syndrome. Blood 72:1849
Elenitoba-Johnson KSJ, Jaffe ES (1997) Lymphoproliferative disorders associated with congenital immunodeficiencies. Semin Diagn Pathol 14: 35
Emile JF, Durandy A, Le Deist F, Fischer A, Brousse N (1997) Epidermal Langerhans' cells in children with primary T-cell immune deficiencies. J Pathol 183: 70
Facchetti F, De Wolf-Peeters C, Van den Oord JJ, De Vos R, Desmet VJ (1988) Plasmacytoid T cells: a cell population normally present in the reactive lymph node. An immunohistochemical and electronmicroscopic study. Hum Pathol 19:1085
Facchetti F, De Wolf-Peeters C, Van den Oord JJ, Meijer CJLM, Pals ST, Desmet VJ (1989) Anti-high endothelial venule monoclonal antibody HECA-452 recognizes plasmacytoid T cells and delineates an “extranodular” compartment in the reactive lymph node. Immunol Lett 20: 277
Facchetti F, Appiani C, Salvi L, Levy J, Notarangelo LD (1995) Immunohistologic analysis of ineffective CD40-CD40 ligand interaction in lymphoid tissues from patients with X-linked immunodeficiency with Hyper-IgM. J Immunol 154: 6624
Facchetti F, Blanzuoli L, Vermi W Notarangelo LD, Giliani S, Fiorini M, Fasth A, Stewart DM, Nelson DL (in press) Defective actin polymerization in EBV-transformed B-cell lines from patients with the Wiskott-Aldrich syndrome. J Pathol
Filipovich AH, Mathur A, Kamat D, Kersey JH, Shapiro RS (1994) Lymphoproliferative disorders and other tumors complicating immunodeficiencies. Immunodeficiency 5: 91
Fischer A (1993) Primary T cell immudeficiencies. Curr Opin Immunol 5:569
Fossum SW, Ford WL (1985) The organization of cell populations wityhin lymph nodes: their origin, life history and functional relationships. Histopathology 9: 469
Gallego MD, Santamaría M, Peña J, Molina IJ (1997) Defective actin reorganization and polymerization of Wiskott-Aldrich T cells in response to CD3-mediated stimulation. Blood 90: 3089
Gosseye S, Diebold N, Griscelli C, Nezelof C (1983) Severe combined immunodeficiency disease: a pathological analysis of 26 cases. Clin Immunol Immunopathol 29:58
Heymer B, Niethammer D, Spanel M, Galle J, Kleihauer E, Haferkamp E (1977) Pathomorphology of humoral, cellular and combined primary immunodeficiencies. Virchows Arch [A] 374:87
Huber J, Zegers BJM, Schuurman HJ (1992) Pathology of congenital immunodeficiencies. Semin Diagn Pathol 9:31
Jouan H, Le Deist F, Nezelof C (1987) Omenn's syndrome — Pathologic arguments in favor of a graft versus host pathogenesis: a report of nine cases. Hum Pathol 18: 1101
Kawai T, Kawano K (1973) Immunopathology of primary immunodeficiency diseases. Acta Pathol Jpn 23:887
Korthäuer U, Graf D, Mages HW, Brière F, Padayachee M, Malcolm S, Ugazio AG, Notarangelo LD, Levinsky RJ, Kroczek RA (1993) Defective expression of T cell CD40 ligand causes X-linked immunodeficiency with hyper IgM. Nature 361:539
Kuijpers KC, Dongen JM van, Burg P van den, Roos MT, Vonk J, Abrev R de, Korte D de, Noesel CJM van, Weening RS, Lier RAW van (1992) A combined immunodeficiency with olygoclonal CD8+, vβ3 expressing, cytotoxic T lymphocytes in the peripheral blood. J Immunol 149: 3403
Lonsdale D, Deodhar SD, Mercer RD (1967) Familial granulocytopenia and associated immunoglobulin abnormality. J Pediatr 71:790
Luscieti P, Hubschmid T, Cottier H, Hess MV, Sobin LH (1980) Human lymph node morphology as a function of age and site. J Clin Pathol 33:454
Macchi P, Villa A, Giliani S, Sacco MG, Frattini A, Porta F, Ugazio AG, Johnson JA, Candotti F, O'Shea JJ, Vezzoni P, Notarangelo LD (1995) Mutation of Jak-3 gene in patients with autosomal severe combined immune deficiency (SCID). Nature 377:65
Manetti R, Annunziato F, Biagiotti R, Giuduzi MG, Piccinni M-P, Giannarini L, Sampognaro S, Parronchi P, Vinante F, Pizzolo G, Maggi E, Romagnari S (1994) CD30 expression by CD8+ T cells producing type 2 helper cytokines. Evidence for large numbers of CD8+CD30+ T cell clones in human immunodeficiency virus infection. J Exp Med 180:2407
Markert ML (1993) Purine nucleoside phosphorylase. In: Rosen FS, Seligmann M (eds) Immunodeficiencies. Harvood Academic, Chur, pp 197–224
Martin JV, Willoughby PB, Giusti V, Price G, Cerezo L (1995) The lymph node pathology of Omenn's syndrome. Am J Surg Pathol 19: 1082
Moreno LA, Gottrand F, Turck D, Monouvrier-Hanu S, Mazingue F, Morisot C, Le Deist F, Ricour C, Nihoul-Feketé C, Debeugny P, Griscelli C, Farriaux JP (1990) Severe combined immunodeficiency syndrome associated with autosomal recessive familial multiple gastrointestinal atresias: study of a family. Am J Med Genet 37:143
Noguchi M, Yi H, Rosenblatt HM, Filipovich AH, Adelstein S, Modi WS, McBride OW, Leonard WJ (1993) Interleukin-2 receptor 7 chain mutation results in X-linked severe combined immunodeficiency in humans. Cell 73:147
Nonoyama S, Hollenbaugh D, Aruffo A, Ledbetter JA, Ochs HD (1993) B cell activation via CD40 is required for specific antibody production by antigen-stimulated human B cells. J Exp Med 178:1097
Notarangelo LD, Duse M, Ugazio AG (1992) Immunodeficiency with hyper-IgM (HIM). Immunodefic Rev 3:101
Ochs HD, Davis SD, Mickelson E, Lerner KG, Wedgwood RJ (1974) Combined immunodeficiency and reticuloendotheliosis with eosinophilia. J Pediatr 85:463
Omenn GS (1965) Familial reticuloendotheliosis with eosinophilia. N Engl J Med 273:427
Park SY, Saito K, Takahashi T, Osawa M, Arase H, Hirayama N, Miyake K, Nakauchi H, Shirasawa T, Saito T (1995) Developmental defects of lymphoid cells in Jak3 kinase-deficient mice. Immunity 3:771
Parott DMV, Sousa MAB de (1966) Changes in the thymus dependent areas of lymph nodes after immunological stimulation. Nature 212:1316
Perez-Atayde AR, Rosen FS (1995) Pathology of the primary immunodeficiency disease. In: Colvin RB, McCluskey (eds) Diagnostic immunopathology. Raven Press, New York, pp 241–259
Ratech H, Hirshhorn R, Greco MA (1989) Pathologic findings in adenosine deaminase deficient-severe combined immunodeficiency. Thymus, spleen, lymph node, and gastrointestinal tract lymphoid tissue alterations. Am J Pathol 135: 1145
Remold-O'Donnel E, Colley J, Shcherbina A, Hagemann TL, Kwan SP, Kenney DM, Rosen FS (1997) Variable expression of WASP in B cell lines of Wiskott-Aldrich syndrome patients. J Immunol 158:4021
Renshaw BR, Fanslow WC III, Armitage RJ, Kampbell KA, Liggit D, Wright B, Davison BL, Maliszewski CR (1994) Humoral immune responses in CD40 ligand-deficient mice. J Exp Med 180: 1889
Resta R, Thompson LF (1997) SCID: the role of adenosine deaminase deficiency. Immunol Today 18: 371
Rosen FS, Wedgwood RJP, Eibl M, et al. (1997) Primary immunodeficiency diseases. Report of a WHO scientific group. Clin Exp Immunol 109(s): 1
Rosenberg YJ, Zack PM, White BD, Papermaster SF, Elkins WR, Eddy GA, Lewis MG (1993) Decline in the CD4+ lymphocyte population in the blood of SIV-infected macaque is not reflected in lymph nodes. AIDS Res Hum Retroviruses 9:639
Røsok BI, Bostad L, Voltervik P, Bjerknes R, Olofsson J, Asjo B, Brinchmann JE (1996) Reduced CD4 cell counts in blood do not reflect CD4 cell depletion in tonsillar tissue in asymptomatic HIV-1 infection. AIDS 10: F35
Rothenberg ME, White FV, Chilmonczyk B, Chatila T (1995) A syndrome involving immunodeficiency and multiple intestinal atresias. Immunodeficiency 5:171
Ruco LP, Stopacciaro A, Pezzella F, Mirolo M, Uccini S, Barsotti P, Cassano AM, Boner AL, Businco L, Di Fazio A, Baroni CD (1985) The Omenn's syndrome: histological, immunohistochemical and ultrastructural evidence for a partial T cell deficiency evolving in an abnormal proliferation of T lympbocytes and S-100+/T-6− Langerhans-like cells. Virchows Arch [A] 407: 69
Sander CA, Medeiros LJ, Weiss LM, Yano T, Sneller MC, Jaffe ES (1992) Lymphoproliferative lesions in patients with common variable immunodeficiency syndrome. Am J Surg Pathol 16:1170
Saunders D, Lucas K, Ismaili J, Wu L, Maraskovsky E, Dunn E, Shortman K (1996) Dendritic cell development in culture from thymic precursor cells in the absence of granulocyte-macrophage colony stimulating factor. J Exp Med 184:2185
Snover DC, Frizzera G, Spector BD, Pery GS, Kersey JH (1981) Wiskott-Aldrich syndrome: histopathologic findings in the lymph nodes and spleens of 15 patients. Hum Pathol 12: 821
Stekel DJ, Parker CE, Nowak MA (1997) A model of lymphocyte recirculation. Immunol Today 18: 216
Stephan JL, Vlekova V, Le Deist F, Blanche S, Donadieu J, De Saint Basile G, Durandy A, Griscelli C, Fisher A (1993) Severe combined immunodeficiency: a retrospective single-center study of clinical presentation and outcome in 117 patients. J Pediatr 123: 564
Stewart DM, Treiber-Held S, Kurman CC, Facchetti F, Notarangelo LD, Nelson DL (1996) Studies of the expression of the Wiskott-Aldrich syndrome protein. J Clin Invest 97:2627
Szabolcs P, Moore MAS, Young JW (1995) Expansion of immunostimulatory dendritic cells among the myeloid progeny of human CD34+ bone marrow precursors cultured witch-kit-ligand, GM-CSF, and THF. J Immunol 154:5851
Tachinami T, Koizumi S, Yachie A, Yamagami M, Yokoi T, Ohno I, Taniguchi N, Takada I, Kawashima A, Okada Y (1990) Immune status in two brothers with Omenn's syndrome: no discernible chimerism on FRCS analysis using a monoclonal antibody specific for a maternally restricted HLA antigen. Am J Pediatr Hematol Oncol 12: 343
Timens W, Boes A, Rozeboom-Uiterwijk T, Poppema S (1988) Immuno-architecture of human fetal lymphoid tissues. Virchows Arch [A] 413:563
Ugazio AG, Duse M, Notarangelo LD, Plebani A, Porta F (1994) Il bambino immunodepresso. Casa Editrice Ambrosiana, Milano
Van der Valk P, Meijer CJLM (1987) The histology of reactive lymph nodes. Am J Surg Pathol 11:866.
Van den Oord JJ, Facchetti F, Delabie J, Wolf-Peeters C de (1990) T lymphocytes in non-neoplastic lymph nodes. In: Grundmann E, Vollmer E (eds) Reaction patterns of the lymph node. Part 1. Cell types and functions. Springer, Berlin Heidelberg New York, pp 149–178
Walker MW, Lovell MA, Kelly TE, Golden W, Saulsbury FT (1993) Multiple areas of intestinal atresia associated with immunodeciency and posttransfusion graft-versus-host disease. J Pediatr 123: 93
Wiskott A (1937) Familiarer, angeborener Morbus Werlhofii? Monatschr Kinderheilk 68: 212
Wolf U (1997) Identical mutations and phenotypic variations. Hum Genet 100: 305
Xu J, Foy TM, Laman JD, Elliott EA, Dunn JJ, Waldschmidt TJ, Elsemore J, Noelle RJ, Flavell RA (1994) Mice deficient for the CD40 ligand. Immunity 1:423
Zhu Q, Zhang M, Blaese RM, Derry JMJ, Junker A, Francke U, Chen SH, Ochs HD (1995) The Wiskott-Aldrich syndrome and X-linked congenital thrombocytopenia are caused by mutation of the same gene. Blood 86: 3797
Zhu Q, Watanabe C, Liu T, Hollenbaugh D, Blaese MR, Kanner SB, Aruffo A, Ochs HD (1997) Wiskott-Aldrich syndrome/X-linked thrombocytopenia: WASP gene mutations, protein expression, and phenotype. Blood 90: 2680
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Facchetti, F., Blanzuoli, L., Ungari, M. et al. Lymph node pathology in primary combined immunodeficiency diseases. Springer Semin Immunopathol 19, 459–478 (1998). https://doi.org/10.1007/BF00792602
Issue Date:
DOI: https://doi.org/10.1007/BF00792602