Role of Chemokine Signalling in the Pathogenesis of Good’s Syndrome-Case Reports, Clinical Characterization from Single-Centre Perspective

Zdziarski, Przemysław; Dworacki, Grzegorz

doi:10.4172/1745-7580.10000119

Cited by 4 publications

(8 citation statements)

References 20 publications

(26 reference statements)

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“…Thymic pathology thus explains the observation of coincident autoimmunity and immunodeficiency, reflecting T cells that are both overreactive to self and underresponsive to pathogens [ 9 ]. In GS, low levels of NK, and CD4+ γδ T cells may be the cause of both low immune surveillance of tumor development and weak clearance of viral infection [ 10 ]. The importance of T cell directing B-cell responses is also apparent in the immunopathology of thymoma, leading to hypogammaglobulinemia as a cardinal manifestation of GS [ 8 11 ].…”

Section: Discussionmentioning

confidence: 99%

“…However, in a study by Przemyslaw and colleagues, 2 observations suggest that thymic pathology is a consequence of central tolerance defects and marrow autoimmune processes rather than the etiology [ 10 11 ]. One, that follow-up of a patient postsurgical excision of a thymoma resulted in neither IgG nor B/NK cell count increase but induces permanent decrease of all subpopulation of T cells during 4-year observation period.…”

Section: Discussionmentioning

confidence: 99%

“…Further, significantly lower IgG level, percentage of peripheral blood B lymphocytes, CD4/CD8 ratio, and expression of CD28 in thymectomized patients have also been described [ 12 ]. Secondly, that B cells in patients with severe form of GS were defective and failed to produce normal amount of Ig even when the influence of T cells was inhibited by immunosuppressive therapy (for example, cyclosporine) [ 10 ]. These suggest that both T- and B-cell defects are not a result of thymic pathology but are a consequence of abnormal differentiation of lymphoid precursor cell subset in the bone marrow [ 8 ].…”

Section: Discussionmentioning

confidence: 99%

“…In recent years, there has also been growing interest in the genetic polymoprhism of cell signaling pathways linked to GS. One such mechanism highlighted is that of weak interaction between CXCL12 (formerly called pre-B-cell growth-stimulating factor), and its ligand CXCR4 on B-cell precursors resulting in low B-cell expression and maturation, and possibly NK cells differentiation arrest [ 10 ]. Another pathway to mention is that of the B-cell activating factor (BAFF): BAFF receptor signaling [ 13 14 ].…”

Section: Discussionmentioning

confidence: 99%

“…Indeed, delineating well-defined clinical and immune parameters with a better understanding of the genetic basis of immune mechanisms will aid in further differentiation of GS from other PIDs and allow better prognostication of disease. One such observation thus far has been the lower expression of NK cells in GS and the association with a poorer prognosis than X-linked agammaglobinaemia (XLA) and common variable immunodeficiency (CVID) [ 10 11 ].…”

Section: Discussionmentioning

confidence: 99%

See 4 more Smart Citations

Atypical presentation of Good syndrome: acute hepatitis from hepatitis B virus reactivation

Lai

Tan

2020

Asia Pacific Allergy

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Good syndrome (GS) is a primary immunodeficiency (PID) that presents in middle aged to older adults with features of thymoma, hypogammaglobulinemia, CD4 T lymphopenia, inverted CD4/CD8+ ratio, and impaired T-cell mitogen proliferative responses. We present a patient, a 62-year-old female, who first presented with disease manifestation of acute hepatitis from hepatitis B virus (HBV) reactivation, which was subsequently complicated by recurrent hospitalizations for recurrent pneumonia and concomitant Helicobacter pylori and cytomegalovirus enteritis. She was later found to have thymoma and hypogammaglobulinemia and was diagnosed with GS. Although the well-known importance of T cell is in directing B-cell responses in the immunopathology of thymoma, low levels of natural killer and CD4+ γδ T cells may also be the cause of both low immune surveillance of tumor development and weak clearance of viral infection. Hence, the temporal sequence of opportunistic infections following HBV reactivation and thymoma discovery may reflect a loss of immune surveillance as the first manifestation of PID.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Atypical presentation of Good syndrome: acute hepatitis from hepatitis B virus reactivation

Lai

Tan

2020

Asia Pacific Allergy

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When the Good Syndrome Goes Bad: A Systematic Literature Review

Shi

Wang

2021

Front. Immunol.

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BackgroundGood syndrome is a rare adult-onset immunodeficiency characterized by thymoma and hypogammaglobulinemia. Its clinical manifestations are highly heterogeneous, ranging from various infections to autoimmunity.ObjectiveThis study was to summarize patient characteristics, identify prognostic factors and define clinical subgroups of Good syndrome.MethodsA systematic literature review was conducted to include patients with Good syndrome identified in PubMed, Embase and Cochrane databases between January 2010 and November 2020. Logistic and Cox regressions were used to identify prognostic factors impacting outcomes. Clinical subgroups were defined by multiple correspondence analysis and unsupervised hierarchical clustering. A decision tree was constructed to characterize the subgroup placement of cases.ResultsOf 162 patients included in the current study, the median age at diagnosis was 58 years and 51% were male. Type AB was the most common histological subtype of thymoma, and infections as well as concurrent autoimmune disorders were identified in 92.6% and 51.2% patients, respectively. Laboratory workup showed typical findings of combined immunodeficiency. Thymoma status (odds ratio [OR] 4.157, confidence interval [CI] 1.219-14.177, p = 0.023), infections related to cellular immunity defects (OR 3.324, 95% CI 1.100-10.046, p = 0.033), infections of sinopulmonary tract (OR 14.351, 95% CI 2.525-81.576, p = 0.003), central nerve system (OR 6.403, 95% CI 1.205-34.027, p = 0.029) as well as bloodstream (OR 6.917, 95% CI 1.519-31.505, p = 0.012) were independent prognostic factors. The 10-year overall survival was 53.7%. Cluster analysis revealed three clinical subgroups with distinct characteristics and prognosis (cluster 1, infections related to cellular immunity defects; cluster 2, infections related to other immunity defects; cluster 3, infections related to humoral and phagocytic immunity defects). A decision tree using infection types (related to humoral and cellular immunity defects) could place patients into corresponding clusters with an overall correct prediction of 72.2%.ConclusionsInfection type and site were the main prognostic factors impacting survival of patients with Good syndrome. We identified three subgroups within Good syndrome associated with distinct clinical features, which may facilitate the study of underlying pathogenesis as well as development of targeted therapy.

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In-depth blood immune profiling of Good syndrome patients

Torres-Valle,

Aragon,

Silva

et al. 2023

Front. Immunol.

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IntroductionGood syndrome (GS) is a rare adult-onset immunodeficiency first described in 1954. It is characterized by the coexistence of a thymoma and hypogammaglobulinemia, associated with an increased susceptibility to infections and autoimmunity. The classification and management of GS has been long hampered by the lack of data about the underlying immune alterations, a controversy existing on whether it is a unique diagnostic entity vs. a subtype of Common Variable Immune Deficiency (CVID).MethodsHere, we used high-sensitive flow cytometry to investigate the distribution of up to 70 different immune cell populations in blood of GS patients (n=9) compared to age-matched CVID patients (n=55) and healthy donors (n=61).ResultsAll 9 GS patients displayed reduced B-cell counts -down to undetectable levels (<0.1 cells/μL) in 8/9 cases-, together with decreased numbers of total CD4+ T-cells, NK-cells, neutrophils, and basophils vs. age-matched healthy donors. In contrast, they showed expanded TCRγδ+ T-cells (p ≤ 0.05). Except for a deeper B-cell defect, the pattern of immune cell alteration in blood was similar in GS and (age-matched) CVID patients. In depth analysis of CD4+ T-cells revealed significantly decreased blood counts of naïve, central memory (CM) and transitional memory (TM) TCD4+ cells and their functional compartments of T follicular helper (TFH), regulatory T cells (Tregs), T helper (Th)2, Th17, Th22, Th1/Th17 and Th1/Th2 cells. In addition, GS patients also showed decreased NK-cell, neutrophil, basophil, classical monocyte and of both CD1c+ and CD141+ myeloid dendritic cell counts in blood, in parallel to an expansion of total and terminal effector TCRγδ+ T-cells. Interestingly, those GS patients who developed hypogammaglobulinemia several years after the thymoma presented with an immunological and clinical phenotype which more closely resembled a combined immune humoral and cellular defect, with poorer response to immunoglobulin replacement therapy, as compared to those in whom the thymoma and hypogammaglobulinemia were simultaneously detected.DiscussionOur findings provide a more accurate definition of the immune cell defects of GS patients and contribute to a better discrimination among GS patients between those with a pure B-cell defect vs. those suffering from a combined immunodeficiency with important consequences on the diagnosis and management of the disease.

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Role of Chemokine Signalling in the Pathogenesis of Good’s Syndrome-Case Reports, Clinical Characterization from Single-Centre Perspective

Cited by 4 publications

References 20 publications

Atypical presentation of Good syndrome: acute hepatitis from hepatitis B virus reactivation

Atypical presentation of Good syndrome: acute hepatitis from hepatitis B virus reactivation

When the Good Syndrome Goes Bad: A Systematic Literature Review

In-depth blood immune profiling of Good syndrome patients

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