Pulmonary Histopathology Findings in Patients With STAT3 Gain of Function Syndrome

2021 ◽  
pp. 109352662098061
Author(s):  
Nahir Cortes-Santiago ◽  
Lisa Forbes ◽  
Tiphanie P Vogel ◽  
Manuel Silva-Carmona ◽  
John Hicks ◽  
...  
Keyword(s):  
B Cells ◽  
Plasma Cells ◽  
Interstitial Fibrosis ◽  
Small Sample ◽  
Lymphocytic Interstitial Pneumonia ◽  
Lung Histopathology ◽  
Key Driver ◽  
Subepithelial Fibrosis ◽  
Lymphoid Aggregates

Introduction and Aim Multiorgan autoimmunity and interstitial lung disease (ILD) are reported in patients with STAT3 GOF syndrome. Results We present lung histopathology findings in 3 such children, two of whom underwent wedge biopsies with adequate diagnostic material. Wedge biopsies showed interstitial cellular expansion with linear and nodular aggregates of CD8 positive T lymphocytes, plasma cells, and histiocytes; consistent with lymphocytic interstitial pneumonia pattern (LIP). CD4+ T cells and CD20+ B cells were present but infrequent in the interstitium. FOXP3 cells ranged from 0-5%. Focal interstitial and intraalveolar histiocytes were also seen. Neutrophils and eosinophils were rare/absent. Non-occlusive peribronchial lymphoid aggregates showed equal T and B cells; likely reactive in nature. Pulmonary vessels appeared normal without vasculitis or hypertensive change. There was no interstitial or subepithelial fibrosis or organizing pneumonia. Interlobular septa and visceral pleura were unremarkable. Conclusion Children with multi-system autoimmune disorders with ILD should be investigated for STAT3 GOF syndrome. Lung wedge biopsies are more informative than transbronchial biopsies, if a tissue sampling is indicated. CD8 dominant T cell inflammation seems to be a key driver of ILD. Although interstitial fibrosis was not seen in our small sample, longer follow up is needed to understand the natural history.

scholarly journals Absence of B Cells in Brainstem and White Matter Lesions Associates With Less Severe Disease and Absence of Oligoclonal Bands in MS

2021 ◽  
Vol 8 (2) ◽  
pp. e955
Author(s):  
Nina L. Fransen ◽  
Brigit A. de Jong ◽  
Katharina Heß ◽  
Tanja Kuhlmann ◽  
Maria C.J. Vincenten ◽  
...  
Keyword(s):  
B Cells ◽  
White Matter ◽  
B Cell ◽  
Clinical Characteristics ◽  
Plasma Cells ◽  
Severe Disease ◽  
Oligoclonal Bands ◽  
Clinical Cohort ◽  
G Ratio

ObjectiveTo determine whether B-cell presence in brainstem and white matter (WM) lesions is associated with poorer pathological and clinical characteristics in advanced MS autopsy cases.MethodsAutopsy tissue of 140 MS and 24 control cases and biopsy tissue of 24 patients with MS were examined for CD20+ B cells and CD138+ plasma cells. The presence of these cells was compared with pathological and clinical characteristics. In corresponding CSF and plasma, immunoglobulin (Ig) G ratio and oligoclonal band (OCB) patterns were determined. In a clinical cohort of 73 patients, the presence of OCBs was determined during follow-up and compared to status at diagnosis.ResultsIn 34% of active and 71% of mixed active/inactive lesions, B cells were absent, which correlated with less pronounced meningeal B-cell infiltration (p < 0.0001). The absence of B cells and plasma cells in brainstem and WM lesions was associated with a longer disease duration (p = 0.001), less frequent secondary progressive MS compared with relapsing and primary progressive MS (p < 0.0001 and p = 0.046, respectively), a lower proportion of mixed active/inactive lesions (p = 0.01), and less often perivascular T-cell clustering (p < 0.0001). Moreover, a lower CSF IgG ratio (p = 0.006) and more frequent absence of OCBs (p < 0.0001) were noted. In a clinical cohort, numbers of patients without OCBs in CSF were increased at follow-up (27.4%).ConclusionsThe absence of B cells is associated with a favorable clinical and pathological profile. This finding may reflect extremes of a continuum of genetic or environmental constitution, but also a regression of WM humoral immunopathology in the natural course of advanced MS.

scholarly journals Immunohistochemical Detection of Lymphocyte Subpopulations in the Tarsal Joints of Chickens with Experimental Viral Arthritis

1996 ◽  
Vol 33 (3) ◽  
pp. 303-310 ◽  
Author(s):  
T. L. Pertile ◽  
M. M. Walser ◽  
J. M. Sharma ◽  
J. L. Shivers
Keyword(s):  
T Cells ◽  
B Cells ◽  
Plasma Cells ◽  
Chronic Arthritis ◽  
Dendritic Morphology ◽  
Large Numbers ◽  
Activation Level ◽  
Cartilage Cells ◽  
Cryostat Sections ◽  
Lymphoid Aggregates

We characterized the lymphocytes in the tarsal joint synovium of chickens inoculated with an arthrotropic strain of avian reovirus. Cryostat sections of whole joints taken from 2 days to 35 days postinoculation were analyzed using monoclonal antibodies directed against B lymphocytes, T lymphocytes, and chicken Ia antigen. Plasma cells were morphologically identified using stained sections of whole joints. Time-dependent changes were found in the type and number of positively staining cells. Synoviocytes and cells with a dendritic morphology stained positive for Ia in normal joint sections. T cells, mostly CD8 positive, were present in low numbers in acute phase arthritis (2-6 days postinfection) in the perivascular and superficial regions of the synovium. Subacute arthritis (8-14 days postinfection) was characterized by increased numbers of CD4 and CD8 T cells in the perivascular and superficial regions. The perivascular T cells began to organize into aggregates, with IgM-positive B cells and plasma cells on the periphery of these aggregates. Some CD8-positive cells were detected on the surface of the articular cartilage. Cells staining positively for Ia were not lymphocytes. Chronic arthritis (> 14 days postinfection) was characterized by large numbers of T cells in the perivascular and superficial regions, with the CD4-positive T cells found primarly in the lymphoid aggregates of the perivascular regions. IgM-positive B cells were fewer, but more plasma cells, few of which stained positive for IgM, were present. Lymphocytes in chronic arthritis stained positively for Ia. These data suggest that the types, numbers, and activation level of lymphocytes present in the tarsal joints are similar but not identical to those seen in rheumatoid arthritis.

Lymphoid Aggregates of Tolerogenic B Cells Feature in the Dynamic Immunological Landscape of the Uterus from Pre-Pregnancy to Delivery

2019 ◽  
Author(s):  
Marilen Benner ◽  
Dorien Feyaerts ◽  
Celia Cartagena García ◽  
Nurcan İnci ◽  
Sergi Cedó López ◽  
...  
Keyword(s):  
B Cells ◽  
Lymphoid Aggregates

447 Cost-Effectiveness of a 3-Year Tele-OSA Intervention

SLEEP ◽  
2021 ◽  
Vol 44 (Supplement_2) ◽  
pp. A177-A177
Author(s):  
Jaejin An ◽  
Dennis Hwang ◽  
Jiaxiao Shi ◽  
Amy Sawyer ◽  
Aiyu Chen ◽  
...  
Keyword(s):  
Cost Effectiveness ◽  
Willingness To Pay ◽  
Incremental Cost ◽  
Economic Benefits ◽  
Small Sample ◽  
Apnea Hypopnea Index ◽  
Obstructive Sleep ◽  
Group 2 ◽  
The Cost

Abstract Introduction Trial-based tele-obstructive sleep apnea (OSA) cost-effectiveness analyses have often been inconclusive due to small sample sizes and short follow-up. In this study, we report the cost-effectiveness of Tele-OSA using a larger sample from a 3-month trial that was augmented with 2.75 additional years of epidemiologic follow-up. Methods The Tele-OSA study was a 3-month randomized trial conducted in Kaiser Permanente Southern California that demonstrated improved adherence in patients receiving automated feedback messaging regarding their positive airway pressure (PAP) use when compared to usual care. At the end of the 3 months, participants in the intervention group pseudo-randomly either stopped or continued receiving messaging. This analysis included those participants who had moderate-severe OSA (Apnea Hypopnea Index &gt;=15) and compared the cost-effectiveness of 3 groups: 1) no messaging, 2) messaging for 3 months only, and 3) messaging for 3 years. Costs were derived by multiplying medical service use from electronic medical records times costs from Federal fee schedules. Effects were average nightly hours of PAP use. We report the incremental cost per incremental hour of PAP use as well as the fraction acceptable. Results We included 256 patients with moderate-severe OSA (Group 1, n=132; Group 2, n=79; Group 3, n=45). Group 2, which received the intervention for 3 months only, had the highest costs and fewest hours of use and was dominated by the other two groups. Average 1-year costs for groups 1 and 3 were $6035 (SE, $477) and $6154 (SE, $575), respectively; average nightly hours of PAP use were 3.07 (SE, 0.23) and 4.09 (SE, 0.42). Compared to no messaging, messaging for 3 years had an incremental cost ($119, p=0.86) per incremental hour of use (1.02, p=0.03) of $117. For a willingness-to-pay (WTP) of $500 per year ($1.37/night), 3-year messaging has a 70% chance of being acceptable. Conclusion Long-term Tele-OSA messaging was more effective than no messaging for PAP use outcomes but also highly likely cost-effective with an acceptable willingness-to-pay threshold. Epidemiologic evidence suggests that this greater use will yield both clinical and additional economic benefits. Support (if any) Tele-OSA study was supported by the AASM Foundation SRA Grant #: 104-SR-13

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