Subpopulations of cells from bronchoalveolar lavage can predict prognosis in sarcoidosis

Darlington, Pernilla; Kullberg, Susanna; Eklúnd, Anders; Grünewald, Johan

doi:10.1183/13993003.01450-2019

Cited by 11 publications

(7 citation statements)

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“…Eventually, the neutrophil count in BAL may increase in advanced sarcoidosis denoting the presence of pulmonary fibrosis and thus indicating an unfavorable prognosis [ 50 ]. High percentages of CD4 V2.3+ T cells (>10.5%) are associated with a better prognosis [ 51 ]. CD103+CD4+ T cells count as well as CD103+CD4+/CD4 in BALF was also found to be relevant for sarcoidosis diagnosis.…”

Section: Clinical Manifestationsmentioning

confidence: 99%

Sarcoidosis: A Clinical Overview from Symptoms to Diagnosis

Sève

Pachéco

Durupt

et al. 2021

Cells

271

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Sarcoidosis is a multi-system disease of unknown etiology characterized by the formation of granulomas in various organs. It affects people of all ethnic backgrounds and occurs at any time of life but is more frequent in African Americans and Scandinavians and in adults between 30 and 50 years of age. Sarcoidosis can affect any organ with a frequency varying according to ethnicity, sex and age. Intrathoracic involvement occurs in 90% of patients with symmetrical bilateral hilar adenopathy and/or diffuse lung micronodules, mainly along the lymphatic structures which are the most affected system. Among extrapulmonary manifestations, skin lesions, uveitis, liver or splenic involvement, peripheral and abdominal lymphadenopathy and peripheral arthritis are the most frequent with a prevalence of 25–50%. Finally, cardiac and neurological manifestations which can be the initial manifestation of sarcoidosis, as can be bilateral parotitis, nasosinusal or laryngeal signs, hypercalcemia and renal dysfunction, affect less than 10% of patients. The diagnosis is not standardized but is based on three major criteria: a compatible clinical and/or radiological presentation, the histological evidence of non-necrotizing granulomatous inflammation in one or more tissues and the exclusion of alternative causes of granulomatous disease. Certain clinical features are considered to be highly specific of the disease (e.g., Löfgren’s syndrome, lupus pernio, Heerfordt’s syndrome) and do not require histological confirmation. New diagnostic guidelines were recently published. Specific clinical criteria have been developed for the diagnosis of cardiac, neurological and ocular sarcoidosis. This article focuses on the clinical presentation and the common differentials that need to be considered when appropriate.

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Section: Clinical Manifestationsmentioning

confidence: 99%

Sarcoidosis: A Clinical Overview from Symptoms to Diagnosis

Sève

Pachéco

Durupt

et al. 2021

Cells

271

144

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“…How a presumed antigen is presented to the T-cells in sarcoidosis seems to play a role for the disease course. There is a correlation with HLA-DRB1*03 and subtypes of *13 and elevated levels of CD4+ Vα2.3+ T-cells in BALF [23]. Furthermore, the majority of patients with LS have either HLA-DRB1*03 and/or DRB3*01, in turn associated with good prognosis [25].…”

Section: Discussionmentioning

confidence: 99%

“…The good prognosis in patients with CD4+ Va2.3+ T cells may indicate that precisely these T-cells for unknown reasons are particularly effective in their immune response to and elimination of such a potential antigen. Thus, the percentage of CD4+ Vα2.3+ T-cells in BALF may also serve as a prognostic marker as the proportion of patients with resolving disease increases gradually with increased proportions of CD4+ Vα2.3+ T-cells in BALF [23]. LS patients have the highest levels of CD4+ Vα2.3+ T-cells as well as the best prognosis and are in addition found to have very few extrapulmonary manifestations (EN and ankle arthritis excluded) [24].…”

Section: Discussionmentioning

confidence: 99%

Lung CD4+ Vα2.3+ T-cells in sarcoidosis cohorts with Löfgren’s syndrome

et al. 2020

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Background: Sarcoidosis is diagnosed by a combination of typical clinical and radiological findings together with biopsy proof of non-caseating epithelioid cell granulomas in affected tissues and/or the cell distribution in bronchoalveolar lavage fluid (BALF). We aimed at investigating the usefulness of measuring the proportion of T-cell receptor (TCR) CD4+ Vα2.3+ T-cells in BALF as an additive marker to CD4/CD8-ratio to confirm the diagnosis. Methods: From a register consisting of 749 sarcoidosis patients [Löfgren's syndrome (LS) n = 274, non-LS n = 475] with information on Vα2.3+ T-cells, an expansion of CD4+ Vα2.3+ T-cells (CD4+ Vα2.3+ T cells > 10.5% in BALF) was seen in 268 (36%). Controls were healthy volunteers (n = 69) and patients with other pulmonary conditions (n = 39), investigated because of suspicion of sarcoidosis. Results: A proportion of CD4+ Vα2.3+ T-cells in BALF > 10.5% was highly specific for sarcoidosis, with a specificity of 97% and with a sensitivity of 36% (p < 0.0001). Receiver operating characteristic (ROC) curves show that testing for CD4+ Vα2.3+ T-cells in BALF was a more useable test in individuals with LS [area under the curve (AUC) 0.82, p < 0.0001] compared to the whole patient group (AUC 0.64, p < 0.0001). Conclusion: In this study, we show that an increased proportion of CD4+ Vα2.3+ T-cells in BALF is highly specific for sarcoidosis. This suggests that this T-cell subset could be used as an additional tool to the CD4/CD8-ratio to support the sarcoidosis diagnosis, particularly in patients with LS but also in patients with non-LS.

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“…The core of the sarcoid granuloma consists predominantly of activated CD4 + T helper (CD4 + Th) lymphocytes with rare scattered CD8 + T cells and B cells in the periphery ( 157 ). The adaptive immune response in sarcoidosis is a predominant CD4 + type 1 helper (CD4 + Th1) response ( 181 ). Activated alveolar CD4 + T-lymphocytes produce high levels of IFN-γ, IL-2, and TNF-α as well as high levels of IL-12 and 1L-18 which skew the immune response toward a Th1 pathway and cause increased expression of Th1-associated chemokines CXCR3 and CCR5 which amplify the Th1-oriented response ( 96 , 157 , 182 , 183 ).…”

Section: The Immunopathogenesis Of Sarcoidosis As It Influences Thera...mentioning

confidence: 99%

Sarcoidosis: Updates on therapeutic drug trials and novel treatment approaches

et al. 2022

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Sarcoidosis is a systemic granulomatous inflammatory disease of unknown etiology. It affects the lungs in over 90% of patients yet extra-pulmonary and multi-organ involvement is common. Spontaneous remission of disease occurs commonly, nonetheless, over 50% of patients will require treatment and up to 30% of patients will develop a chronic progressive non-remitting disease with marked pulmonary fibrosis leading to significant morbidity and death. Guidelines outlining an immunosuppressive treatment approach to sarcoidosis were recently published, however, the strength of evidence behind many of the guideline recommended drugs is weak. None of the drugs currently used for the treatment of sarcoidosis have been rigorously studied and prescription of these drugs is often based on off-label” indications informed by experience with other diseases. Indeed, only two medications [prednisone and repository corticotropin (RCI) injection] currently used in the treatment of sarcoidosis are approved by the United States Food and Drug Administration. This situation results in significant reimbursement challenges especially for the more advanced (and often more effective) drugs that are favored for severe and refractory forms of disease causing an over-reliance on corticosteroids known to be associated with significant dose and duration dependent toxicities. This past decade has seen a renewed interest in developing new drugs and exploring novel therapeutic pathways for the treatment of sarcoidosis. Several of these trials are active randomized controlled trials (RCTs) designed to recruit relatively large numbers of patients with a goal to determine the safety, efficacy, and tolerability of these new molecules and therapeutic approaches. While it is an exciting time, it is also necessary to exercise caution. Resources including research dollars and most importantly, patient populations available for trials are limited and thus necessitate that several of the challenges facing drug trials and drug development in sarcoidosis are addressed. This will ensure that currently available resources are judiciously utilized. Our paper reviews the ongoing and anticipated drug trials in sarcoidosis and addresses the challenges facing these and future trials. We also review several recently completed trials and draw lessons that should be applied in future.

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Subpopulations of cells from bronchoalveolar lavage can predict prognosis in sarcoidosis

Cited by 11 publications

References 11 publications

Sarcoidosis: A Clinical Overview from Symptoms to Diagnosis

Sarcoidosis: A Clinical Overview from Symptoms to Diagnosis

Lung CD4+ Vα2.3+ T-cells in sarcoidosis cohorts with Löfgren’s syndrome

Sarcoidosis: Updates on therapeutic drug trials and novel treatment approaches

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