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Decrease in putative circulating B1 cells in common variable immunodeficiency
ABSTRACTS
Blood mononuclear cell stimulation analyses with cytokine bead array revealed normal IL-12p40 production and IFN-g production in response to exogenous IL-12. Both patients had normal tumour necrosis factor-a (TNF-a) production in response to IFN-g that was remarkably abrogated in the presence of autologous serum. By ELISA, both patients had high titre (>1:5000) anti-IFN-g IgG in the serum. The patients’ IgG inhibited IFN-g-induced MHC class II protein upregulation on CD14þ monocytes. Targeted B cell depletion with rituximab has started for one patient. Autoantibodies against cytokines may disrupt normal immunity and predispose to more severe and resistant NTM disease. In the latter circumstances, screening for anti-IFN-g autoantibodies may clarify the pathophysiology and allow targeted therapy.
AA AMYLOIDOSIS IN NEW CALEDONIA: AN UPDATE Cazorla Ce´cile, Barber Chantal and Quirin Nicolas Centre Hospitalier Territorial de Nouvelle Cale´donie, Noume´a Aim: Creation of AA amyloidosis register in New Caledonia, French Island, South Pacific. Method: Retrospective study between 2008 and 2012. Results: 54 cases of AA amyloidosis were found in 5 years with an incidence of 4.3/100,000/year. Median age is 65 and sex ratio 1,16. 57% are Melanesians, 24% Polynesians and 7% Europeans. Mortality rate is 50%, and in 15% amyloidosis is directly responsible for the death. Chronic underlying diseases distribute as follows: bronchial dilatation 41%, gout 22%. For 31% no inflammatory underlying condition is found. In 54% amyloidosis is complicated with renal, 48% digestive and 7% cardiac involvement. Discussion: Gout is overrepresented in New Caledonia and AA amyloidosis prevalence is three times more frequent than in large occidental studies. A retrospective study started in January 2013 to determine undefined underlying disease in 1/3 of AA amyloidosis cases. The impact of chronic inflammation control in patient suffering from gout will be evaluated too. References 1. Lachmann HJ, Goodman HJ, Gilbertson JA, et al. Natural history and outcome in systemic AA amyloidosis. N Eng J Med 2007; 356: 2361–71. 2. Guma M, Baye´s B, Bonet J, et al. Gout and secondary amyloid. Clin Rheumatol 1999; 18: 54–5. 3. Soulatzky AM. L’amylose en Nouvelle Cale´donie: une premie`re approche. (Thesis.) France, 2007.
INVESTIGATION OF TUMOUR-INFILTRATING T CELLS AND RANK/RANKL SIGNALLING IN BREAST CANCER Elizabeth Thomas1,2, Tim J. Miller1, Kim Cheah3, Tracey Lee-Pullen1,2, Jiake Xu4 and Christobel Saunders1,2 1St John of God Subiaco Hospital, 2The University of Western Australia School of Surgery, 3St John of God Pathology, and 4The University of Western Australia School of Pathology and Laboratory Medicine, WA, Australia Aims: First, to investigate the prognostic significance of T cell subsets and RANK/RANKL signalling in the primary tumour of locally advanced breast cancer (LABC) and metastatic breast cancer patients. Second, to investigate the predictive significance of a relationship between clinical response to the anti-RANKL monoclonal antibody denosumab and immunopathological features of the tumour cells.
S97
Methods: Multiplex immunohistochemistry (IHC; Biocare) is used to assess the marker pairs CD4/CD8, RANK/PR and RANKL/FOXP3 in 84 patients in full-face serial sections and 60 patients in tissue microarrays with LABC or metastatic breast cancer. Aperio ImageScope software and ImageJ digital cellcounting algorithms are used to quantify total marker-positive cells as a percentage of total cells. Results: Statistical analysis of data collected so far shows an independent positive trend between the presence of FOXPþ T cells or CD4þ cells, but not CD8þ T cells, and shorter disease free survival (DFS) and overall survival (OS) (p ¼ 0.089). Discussion: Previous research on T cell infiltration and breast cancer outcomes has produced conflicting data. Our data demonstrate evidence on a large, targeted cohort on the relevance of the presence of different T cell subsets and outcome. This may represent a novel diagnostic tool.
DECREASE IN PUTATIVE CIRCULATING B1 CELLS IN COMMON VARIABLE IMMUNODEFICIENCY Kata Kraljevic1, Sue Wong2 and David Fulcher1,2 1University of Sydney, Camperdown, and 2Pathology West, Westmead Hospital, Westmead, Sydney, NSW, Australia B1 cells are characterised by production of natural antibodies and by production of IgM without T-cell help. B1 cells, clearly defined in mice, have recently had a human counterpart proposed defined by the phenotype CD20þ/CD27þ/CD43þ/CD70 – . Mice lacking B1 cells are susceptible to Streptococcus pneumonia infection, raising the possibility that these cells might be relevant in human immunodeficiency conditions. Common variable immunodeficiency (CVID) is a clinically heterogeneous disease with variable defects in antibody formation and memory B-cell generation, and a subsequent susceptibility to respiratory and gastrointestinal infections. This study examined circulating B1 cells in CVID patients (n ¼ 27) and compared it to age-matched control cohorts (n ¼ 28). There was a 60–70% decrease in B1 cells in CVID (0.039% of lymphocytes) compared with controls (0.110% of lymphocytes, p ¼ 0.0012). Although CVID patients lacking CD27þ memory B cells showed the lowest B1 proportions, the relative deficiency appeared otherwise independent of memory B cells, and was also independent of age. Amongst CVID patients, there was a striking positive correlation between the B1 cell proportion and IgM levels (p < 0.0001). Patients with CVID have fewer circulating phenotypic B1 cells, which may be relevant in understanding IgM regulation and thus their susceptibility to infection.
DIAGNOSTIC UTILITY OF UNIDENTIFIED PRECIPITIN LINE (UPL) Adeloisa Pajaro1, Peter Roberts-Thomson1,2 and Tony Nikoloutsopoulos2 1Department of Allergy and Clinical Immunology, Flinders Medical Centre, and 2SA Pathology, Flinders Medical Centre, SA, Australia Background: Unidentified precipitin line (UPL) is a line which does not characterise with known ENA antibodies. Currently, the clinical significance of UPL is uncertain.
Copyright © Royal College of pathologists of Australasia. Unauthorized reproduction of this article is prohibited.
Blood mononuclear cell stimulation analyses with cytokine bead array revealed normal IL-12p40 production and IFN-g production in response to exogenous IL-12. Both patients had normal tumour necrosis factor-a (TNF-a) production in response to IFN-g that was remarkably abrogated in the presence of autologous serum. By ELISA, both patients had high titre (>1:5000) anti-IFN-g IgG in the serum. The patients’ IgG inhibited IFN-g-induced MHC class II protein upregulation on CD14þ monocytes. Targeted B cell depletion with rituximab has started for one patient. Autoantibodies against cytokines may disrupt normal immunity and predispose to more severe and resistant NTM disease. In the latter circumstances, screening for anti-IFN-g autoantibodies may clarify the pathophysiology and allow targeted therapy.
AA AMYLOIDOSIS IN NEW CALEDONIA: AN UPDATE Cazorla Ce´cile, Barber Chantal and Quirin Nicolas Centre Hospitalier Territorial de Nouvelle Cale´donie, Noume´a Aim: Creation of AA amyloidosis register in New Caledonia, French Island, South Pacific. Method: Retrospective study between 2008 and 2012. Results: 54 cases of AA amyloidosis were found in 5 years with an incidence of 4.3/100,000/year. Median age is 65 and sex ratio 1,16. 57% are Melanesians, 24% Polynesians and 7% Europeans. Mortality rate is 50%, and in 15% amyloidosis is directly responsible for the death. Chronic underlying diseases distribute as follows: bronchial dilatation 41%, gout 22%. For 31% no inflammatory underlying condition is found. In 54% amyloidosis is complicated with renal, 48% digestive and 7% cardiac involvement. Discussion: Gout is overrepresented in New Caledonia and AA amyloidosis prevalence is three times more frequent than in large occidental studies. A retrospective study started in January 2013 to determine undefined underlying disease in 1/3 of AA amyloidosis cases. The impact of chronic inflammation control in patient suffering from gout will be evaluated too. References 1. Lachmann HJ, Goodman HJ, Gilbertson JA, et al. Natural history and outcome in systemic AA amyloidosis. N Eng J Med 2007; 356: 2361–71. 2. Guma M, Baye´s B, Bonet J, et al. Gout and secondary amyloid. Clin Rheumatol 1999; 18: 54–5. 3. Soulatzky AM. L’amylose en Nouvelle Cale´donie: une premie`re approche. (Thesis.) France, 2007.
INVESTIGATION OF TUMOUR-INFILTRATING T CELLS AND RANK/RANKL SIGNALLING IN BREAST CANCER Elizabeth Thomas1,2, Tim J. Miller1, Kim Cheah3, Tracey Lee-Pullen1,2, Jiake Xu4 and Christobel Saunders1,2 1St John of God Subiaco Hospital, 2The University of Western Australia School of Surgery, 3St John of God Pathology, and 4The University of Western Australia School of Pathology and Laboratory Medicine, WA, Australia Aims: First, to investigate the prognostic significance of T cell subsets and RANK/RANKL signalling in the primary tumour of locally advanced breast cancer (LABC) and metastatic breast cancer patients. Second, to investigate the predictive significance of a relationship between clinical response to the anti-RANKL monoclonal antibody denosumab and immunopathological features of the tumour cells.
S97
Methods: Multiplex immunohistochemistry (IHC; Biocare) is used to assess the marker pairs CD4/CD8, RANK/PR and RANKL/FOXP3 in 84 patients in full-face serial sections and 60 patients in tissue microarrays with LABC or metastatic breast cancer. Aperio ImageScope software and ImageJ digital cellcounting algorithms are used to quantify total marker-positive cells as a percentage of total cells. Results: Statistical analysis of data collected so far shows an independent positive trend between the presence of FOXPþ T cells or CD4þ cells, but not CD8þ T cells, and shorter disease free survival (DFS) and overall survival (OS) (p ¼ 0.089). Discussion: Previous research on T cell infiltration and breast cancer outcomes has produced conflicting data. Our data demonstrate evidence on a large, targeted cohort on the relevance of the presence of different T cell subsets and outcome. This may represent a novel diagnostic tool.
DECREASE IN PUTATIVE CIRCULATING B1 CELLS IN COMMON VARIABLE IMMUNODEFICIENCY Kata Kraljevic1, Sue Wong2 and David Fulcher1,2 1University of Sydney, Camperdown, and 2Pathology West, Westmead Hospital, Westmead, Sydney, NSW, Australia B1 cells are characterised by production of natural antibodies and by production of IgM without T-cell help. B1 cells, clearly defined in mice, have recently had a human counterpart proposed defined by the phenotype CD20þ/CD27þ/CD43þ/CD70 – . Mice lacking B1 cells are susceptible to Streptococcus pneumonia infection, raising the possibility that these cells might be relevant in human immunodeficiency conditions. Common variable immunodeficiency (CVID) is a clinically heterogeneous disease with variable defects in antibody formation and memory B-cell generation, and a subsequent susceptibility to respiratory and gastrointestinal infections. This study examined circulating B1 cells in CVID patients (n ¼ 27) and compared it to age-matched control cohorts (n ¼ 28). There was a 60–70% decrease in B1 cells in CVID (0.039% of lymphocytes) compared with controls (0.110% of lymphocytes, p ¼ 0.0012). Although CVID patients lacking CD27þ memory B cells showed the lowest B1 proportions, the relative deficiency appeared otherwise independent of memory B cells, and was also independent of age. Amongst CVID patients, there was a striking positive correlation between the B1 cell proportion and IgM levels (p < 0.0001). Patients with CVID have fewer circulating phenotypic B1 cells, which may be relevant in understanding IgM regulation and thus their susceptibility to infection.
DIAGNOSTIC UTILITY OF UNIDENTIFIED PRECIPITIN LINE (UPL) Adeloisa Pajaro1, Peter Roberts-Thomson1,2 and Tony Nikoloutsopoulos2 1Department of Allergy and Clinical Immunology, Flinders Medical Centre, and 2SA Pathology, Flinders Medical Centre, SA, Australia Background: Unidentified precipitin line (UPL) is a line which does not characterise with known ENA antibodies. Currently, the clinical significance of UPL is uncertain.
Copyright © Royal College of pathologists of Australasia. Unauthorized reproduction of this article is prohibited.