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OR.54. Specific Antibody Deficiency in a Patient with Chronic Mucocutaneous Candidiasis
S24
Abstracts
Giant cell arteritis specifically targets medium and large human arteries with granulomatous infiltrates accumulating in the medial wall layer. Vascular dendritic cells (vasDC) localized at the adventitia-media border are critical in recruiting and stimulating T-cells. To examine their role in determining T-cell effector functions in vasculitis we studied vasDC-T-cell interactions in an in vitro organ culture system and by adoptively transferring human T-cells into SCID mice engrafted with human arteries. Resting vasDC do not attract or stimulate alloreactive CD4 T-cells. Following triggering with TLR ligands, vasDC recruit T-cells to the vessel wall and induce their in situ activation. To understand their role in directing T-cell effector functions we compared the effect of vasDC activation via two distinct TLR ligands, LPS (binding TLR4) and flagellin (binding TLR5). In the organ cultures and the human artery-chimeras TRL4 and TRL5 triggering were equally efficient in inducing T-cell recruitment to the blood vessel. Immunohistochemistry and qPCR for TCR sequences confirmed T-cell accumulation in the arterial wall. However, LPS pretreatment resulted in Tcells invading into the medial layer (p = 0.03) whereas flagellin pretreatment caused T-cells to accumulate in the adventitia (p = 0.01). Human T-cells isolated from explanted artery grafts proliferated vigorously independent of the mechanism of vasDC triggering. Quantification of IFNg and CD40L transcripts in explanted tissues demonstrated equal levels of T-cell activation (p = 0.01 and 0.03 Con vs LPS or flag, respectively; p = 0.11 LPS vs flag). However, the chemokine profiles were distinct with CCL19 dominating TLR4-, and CCL20 induction following TLR5-mediated DC activation. We conclude that TLRlicensed vasDC selectively recruit, stimulate and instruct T-cells and that TLR4 and TLR5 ligands induce distinct patterns of vascular inflammation. doi:10.1016/j.clim.2006.04.209
#2403- B-Cell/Autoantibody Saturday, June 3 3:30—5:30 pm OR.54. Specific Antibody Deficiency in a Patient with Chronic Mucocutaneous Candidiasis. Oner Ozdemir, Ricardo Sorensen. Department of Pediatrics, Div. of Allergy/Immunology, Louisiana State University Health Sciences Center, New Orleans, LA. Background: Chronic mucocutaneous candidiasis (CMC) is characterized by persistent yeast infection, usually with Candida albicans. CMC patients with selective antibody deficiency(SAD) rarely reported. Here, we describe a CMC patient having SAD with recurrent otitis media and pneumonia. Patient/Methods: 23-year-old Caucasian female suffered from persistent thrush, failure to thrive, recurrent otitis media and pneumonia since 6 weeks of age. Pneumonia episodes decreased with IVIG at age 6. At age 11, she developed persistent tinea capitis and severe Coomb’s(+) hemolytic anemia. Four months later, she was
very fatigued, slightly jaundiced and had pericardial effusion. At age 12, she developed severe candida esophagitis. She had PBMN stem cell transplantation twice without reconstitution. At age 18, she was diagnosed with SLE due to clinical and laboratory findings. At age 23, she was admitted due to Coomb’s(+) hemolytic anemia second time and died from multiple organ failure. Results: CBC, CMP, immunoglobulins, antigen-mitogen responses, T-/Bcell numbers, complement levels, NBT and sweat test were normal at diagnosis. CMC was proven by cutaneous anergy as well as clinical findings but her lymphoproliferative responses to Candida was normal. At age 4, she was noted to have poor antibody response to pneumococcal polysaccharide antigen, but normal to diphtheria and tetanus. Low IgA, IgG2 and C4 levels were detected at age 17. Low T- and NK-cell counts were found at age 18. Candida albicans was isolated from skin and seen on KOH preparations. Ear drainage cultures grew MRSA, Klebsiella pneumonia and Candida parapsilosis. Staph. aureus and Pseudomonas aeruginosa grew in sputum cultures. Conclusion: SAD should be considered in CMC patients with the suggestive clinical and laboratory findings. Keywords: Specific Antibody Deficiency, Chronic Mucocutaneous Candidiasis. doi:10.1016/j.clim.2006.04.210
OR.55. Synovial Follicular Microarchitecture Is Not Related to Antigen-Specific Humoral Responses in Chronic Inflammatory Arthritis. Tineke Cantaert,1 Carla Wijbrandts,1 Rogier Thurlings,1 Bernard Vandooren,2 Leen De Rycke,2 Niek de Vries,1 Paul Tak,1 Dominique Baeten.1 1Division of Clinical Immunology and Rheumatology, Academic Medical Center/ University of Amsterdam, Amsterdam, Netherlands; 2 Department of Rheumatology, University Hospital Ghent, Ghent, Belgium. Objective: Synovitis in rheumatoid arthritis (RA) can present as diffuse, granulomatous, or follicular synovitis. In the last type, B, T and dendritic cells cluster in lymphoid follicle-like structures. Since this specific microarchitecture may promote B-cell maturation and activation, we investigated whether synovial follicles are specific for RA and are related to autoantibody production. Methods: Synovium and serum were obtained from 56 RA and 74 spondyloarthritis (SpA) patients. Histological analysis included follicles, global infiltration, and numbers of T (CD3), B (CD20), and dendritic cells (CD1a). Anti-citrullinated protein antibodies (ACPA) and rheumatoid factor (RF) were determined by anti-CCP ELISA and latex fixation. Results: Lymphoid follicles were equally found in RA and SpA (both 34%). Their presence was independent of disease duration, treatment, or SpA subtype. In RA, follicles were associated with a higher number of inflammatory cells (p = 0.018), CD20+ (p = 0.074) and CD1a+ cells (p = 0.010). Similarly, in SpA follicles were strongly associated with cell infiltration (p b 0.001), CD3+ (p = 0.001) and CD20+ cells (p b 0.001). Surprisingly, however, clinical disease activity was lower in RA patients with than in those without
Abstracts
Giant cell arteritis specifically targets medium and large human arteries with granulomatous infiltrates accumulating in the medial wall layer. Vascular dendritic cells (vasDC) localized at the adventitia-media border are critical in recruiting and stimulating T-cells. To examine their role in determining T-cell effector functions in vasculitis we studied vasDC-T-cell interactions in an in vitro organ culture system and by adoptively transferring human T-cells into SCID mice engrafted with human arteries. Resting vasDC do not attract or stimulate alloreactive CD4 T-cells. Following triggering with TLR ligands, vasDC recruit T-cells to the vessel wall and induce their in situ activation. To understand their role in directing T-cell effector functions we compared the effect of vasDC activation via two distinct TLR ligands, LPS (binding TLR4) and flagellin (binding TLR5). In the organ cultures and the human artery-chimeras TRL4 and TRL5 triggering were equally efficient in inducing T-cell recruitment to the blood vessel. Immunohistochemistry and qPCR for TCR sequences confirmed T-cell accumulation in the arterial wall. However, LPS pretreatment resulted in Tcells invading into the medial layer (p = 0.03) whereas flagellin pretreatment caused T-cells to accumulate in the adventitia (p = 0.01). Human T-cells isolated from explanted artery grafts proliferated vigorously independent of the mechanism of vasDC triggering. Quantification of IFNg and CD40L transcripts in explanted tissues demonstrated equal levels of T-cell activation (p = 0.01 and 0.03 Con vs LPS or flag, respectively; p = 0.11 LPS vs flag). However, the chemokine profiles were distinct with CCL19 dominating TLR4-, and CCL20 induction following TLR5-mediated DC activation. We conclude that TLRlicensed vasDC selectively recruit, stimulate and instruct T-cells and that TLR4 and TLR5 ligands induce distinct patterns of vascular inflammation. doi:10.1016/j.clim.2006.04.209
#2403- B-Cell/Autoantibody Saturday, June 3 3:30—5:30 pm OR.54. Specific Antibody Deficiency in a Patient with Chronic Mucocutaneous Candidiasis. Oner Ozdemir, Ricardo Sorensen. Department of Pediatrics, Div. of Allergy/Immunology, Louisiana State University Health Sciences Center, New Orleans, LA. Background: Chronic mucocutaneous candidiasis (CMC) is characterized by persistent yeast infection, usually with Candida albicans. CMC patients with selective antibody deficiency(SAD) rarely reported. Here, we describe a CMC patient having SAD with recurrent otitis media and pneumonia. Patient/Methods: 23-year-old Caucasian female suffered from persistent thrush, failure to thrive, recurrent otitis media and pneumonia since 6 weeks of age. Pneumonia episodes decreased with IVIG at age 6. At age 11, she developed persistent tinea capitis and severe Coomb’s(+) hemolytic anemia. Four months later, she was
very fatigued, slightly jaundiced and had pericardial effusion. At age 12, she developed severe candida esophagitis. She had PBMN stem cell transplantation twice without reconstitution. At age 18, she was diagnosed with SLE due to clinical and laboratory findings. At age 23, she was admitted due to Coomb’s(+) hemolytic anemia second time and died from multiple organ failure. Results: CBC, CMP, immunoglobulins, antigen-mitogen responses, T-/Bcell numbers, complement levels, NBT and sweat test were normal at diagnosis. CMC was proven by cutaneous anergy as well as clinical findings but her lymphoproliferative responses to Candida was normal. At age 4, she was noted to have poor antibody response to pneumococcal polysaccharide antigen, but normal to diphtheria and tetanus. Low IgA, IgG2 and C4 levels were detected at age 17. Low T- and NK-cell counts were found at age 18. Candida albicans was isolated from skin and seen on KOH preparations. Ear drainage cultures grew MRSA, Klebsiella pneumonia and Candida parapsilosis. Staph. aureus and Pseudomonas aeruginosa grew in sputum cultures. Conclusion: SAD should be considered in CMC patients with the suggestive clinical and laboratory findings. Keywords: Specific Antibody Deficiency, Chronic Mucocutaneous Candidiasis. doi:10.1016/j.clim.2006.04.210
OR.55. Synovial Follicular Microarchitecture Is Not Related to Antigen-Specific Humoral Responses in Chronic Inflammatory Arthritis. Tineke Cantaert,1 Carla Wijbrandts,1 Rogier Thurlings,1 Bernard Vandooren,2 Leen De Rycke,2 Niek de Vries,1 Paul Tak,1 Dominique Baeten.1 1Division of Clinical Immunology and Rheumatology, Academic Medical Center/ University of Amsterdam, Amsterdam, Netherlands; 2 Department of Rheumatology, University Hospital Ghent, Ghent, Belgium. Objective: Synovitis in rheumatoid arthritis (RA) can present as diffuse, granulomatous, or follicular synovitis. In the last type, B, T and dendritic cells cluster in lymphoid follicle-like structures. Since this specific microarchitecture may promote B-cell maturation and activation, we investigated whether synovial follicles are specific for RA and are related to autoantibody production. Methods: Synovium and serum were obtained from 56 RA and 74 spondyloarthritis (SpA) patients. Histological analysis included follicles, global infiltration, and numbers of T (CD3), B (CD20), and dendritic cells (CD1a). Anti-citrullinated protein antibodies (ACPA) and rheumatoid factor (RF) were determined by anti-CCP ELISA and latex fixation. Results: Lymphoid follicles were equally found in RA and SpA (both 34%). Their presence was independent of disease duration, treatment, or SpA subtype. In RA, follicles were associated with a higher number of inflammatory cells (p = 0.018), CD20+ (p = 0.074) and CD1a+ cells (p = 0.010). Similarly, in SpA follicles were strongly associated with cell infiltration (p b 0.001), CD3+ (p = 0.001) and CD20+ cells (p b 0.001). Surprisingly, however, clinical disease activity was lower in RA patients with than in those without