Good's Syndrome Research Articles

Good syndrome combined with multiple microbial pulmonary infections: case report and review of the literature.

Good syndrome (GS), a rare acquired immunodeficiency disorder characterized by thymoma and hypogammaglobulinemia, predisposes individuals to recurrent infections. This study reports a case of a 37-year-old male GS with multiple pulmonary infections and reviews relevant literature. The patient, with a history of thymoma resection, experienced multiple hospitalizations due to lung infections and neutropenia. The alveolar lavage fluid was detected by macro-genomic sequencing (NGS) to detect multiple pathogens, and targeted anti-infective and immunity-enhancing treatments led to improved symptoms and normal neutrophil counts. A literature review of 98 case reports from 2000 to 2023 was conducted, summarizing the associated diseases and pathogens in GS patients. Regular immunoglobulin monitoring in thymoma patients is essential for early GS diagnosis. When empirical antimicrobial therapy fails, mNGS for pathogen detection and targeted therapy are crucial, and regular IVIG injections can reduce infection rates in GS patients.

1166 Thymoma and Good's Syndrome: Analysing the Role of Surgery in a Case Series

Abstract Background Good’s syndrome is a rare paraneoplastic phenomenon with unknown pathogenesis in patients with thymoma. The incidence is 0.15 cases per 100,000 population per year. Patients typically have hypogammaglobulinemia, reduced B cell and CD4+ T cell count, and present with recurrent infections and autoimmune manifestations. Case Summary This case series highlights two patients with Good’s syndrome who underwent thymectomy in a United Kingdom Thoracic Surgery Unit. Patient 1, a 57-year-old female, presented with a history of recurrent infections (including Pneumocystis jiroveci), dysphagia, and dyspnoea. The subsequent discovery of a thymoma led to a diagnosis of Good Syndrome. Patient 2, a 61-year-old male, exhibited recurrent infections and immunological abnormalities, eventually leading to the identification of a thymoma. Both patients were diagnosed in their 5th decade, and shared similar clinical profiles with absent B cells, reduced NK cells, hypogammaglobulinemia, and an anterior thymoma. Preoperatively, they received IVIG transfusions. The surgical intervention involved robotic-assisted thymectomy for both patients. Histopathological assessments classified Patient 1 as T1bNxMxR1 and Patient 2 as T1aNXMXR1 providing insights into the extent of the thymomas. Post-operatively they continue to have prophylactic antibiotics and IVIG and have been reportedly well. Conclusions Patients with Good Syndrome are at significant risk of opportunistic infections and may present repeatedly to medical specialties. Thymoma and its associated symptoms can precede immunodeficiency. Consequently, thorough consideration of this diagnosis, interdisciplinary collaboration, and preoperative planning is vital for the effective management of this extremely rare syndrome. Successful outcomes are achievable through timely IVIG and full surgical resection.

COVID-19 in patients with Good syndrome: report of 4 cases and literature review

Objective: To summarize the clinical characteristics of coronavirus disease 2019 (COVID-19) in patients with Good's syndrome. Methods: We included all cases of COVID-19 in patients with Good's syndrome in the Second Xiangya Hospital of Central South University from January 1, 2023 to August 31, 2023. In addition to our cases, we searched the published literature in Wanfang database and PubMed database using the keywords "Good's syndrome" and "COVID-19". The clinical characteristics, treatment and outcome of the patients were summarized and analyzed. Results: A total of four patients with Good's syndrome complicated by COVID-19 were identified in our hospital, all of them were male, and the days of hospitalization were 17, 23, 7, and 13 days, respectively. Databases were searched for a total of six patients with Good's syndrome complicated by COVID-19, including three females and three males, all foreign patients, with hospitalization days of 12, 22, 13, 25, 21, and 34 days respectively. All ten patients met the diagnostic criteria for severe or critical COVID-19, and three(all middle-aged males) of them died, two from sepsis and one from respiratory failure. They were. Conclusion: COVID-19 in patients with Good's syndrome are prone to develop severe or critical disease and are more likely to be infected with multiple pathogens. Timely immunoglobulin supplementation is the key to treatment.

Somatic variant profiling of a thymoma in Good syndrome

Good syndrome (GS) is a combined immunodeficiency that is associated with thymomas. The cause of the reduction in B-cells in patients with GS may be multifactorial and may include dysregulated T-cell responses. It has been proposed that tumorigenesis in a normal thymus alters thymic epithelial cell function, which leads to attenuated elimination of T-cells autoreactive to B-cells. Although the comprehensive genetic analysis of thymoma has been performed and reported in many articles, the comprehensive genetic analysis specified for GS-related thymoma has not been reported. Herein, we report comprehensive genetic analysis of a thymoma taken from a patient with GS. Oncogenesis-associated genes that may contribute to thymoma development were detected. Additionally, alteration of VCAM1, which is required in the interaction between T-cells and thymic epithelial cells, was observed. Aberrantly expressed VCAM1 in thymic epithelial cells may decrease the efficacy of negative of selection autoreactive T-cells and contribute to autoimmunity to B-cells.

Clinical and genomic evaluations of a persistent fatal SARS-CoV-2 infection in a goods syndrome patient: a case report

The coronavirus disease of 2019 (COVID-19) resulted from an infection by severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) which is the main cause of acute respiratory distress syndrome (ARDS) in global population from 2019 on. It may contribute to higher rate of death among the patients with immunodeficiency based on recent reports. In addition, Good syndrome (GS) as a result of thymoma removal might cause in some long-lasting microbial infections. We described clinical aspects and viral mutations on a case of GS suffering from COVID-19. A 46-year-old man with fever, common respiratory disease symptoms and positive COVID-19 polymerase chain reaction (PCR) test, with the history of thymoma removal surgery was admitted to Masih Daneshvari Hospital, Tehran, Iran. Lung radiographs and oxygen saturation measurement disclosed considerable implication resulted in application of several anti-microbial medication. The delta variant (B.1.617.2 (21 J Clade)) was the strain isolated from the patient by sequencing methods done by the COVID-19 National Reference Laboratory (CNRL), Pasteur Institute of Iran, while the dominant strain circulated mostly among population was Omicron (B.1.1.529) at the time of sampling. Unfortunately, the patient had passed away a month later by sudden respiratory failure progressed in refractory septic shock. Despite the fact that opportunistic infections may lead the GS patients to a major health problematic condition, unusual persistent of infections such as non-dominant variant of SARS-Cov-2 could be observed through the disease timeline. Therefore, a fully screening of thymoma plus intra-host evolution monitoring of SARS-CoV-2 is highly recommended in immunocompromised patients.

Rare disease in the age of artificial intelligence.

The text examines the impact of artificial intelligence (AI) in the context of rare diseases, exploring how patients turn to AI resources for health information, especially in situations where doctor-patient communication is limited. The article features the case of a doctor specializing in clinical psychology and psychotherapy, diagnosed with thymoma and Good's syndrome, who uses AI resources during his illness. The capabilities of five chatbots based on Large Language Models (LLMs), such as GPT-3.5, GPT-4, Bing Chat, Google Bard, and Anthropic Claude are explored. The AIs were queried on various aspects of the disease, from pre-diagnosis and diagnosis to therapeutic, psychological, and caregiver management issues. The responses were evaluated by five experts based on criteria such as: accuracy, relevance, coherence, clarity, practical utility, ethical considerations, empathy, and capacity to respond to questions and concerns. The results indicate consistency in the evaluators' assessments, with generally high scores across all dimensions. Particularly, systems like Bard and GPT-4 received high ratings in terms of information accuracy and the ability to respond to questions and concerns. Bing and Claude were appreciated for their empathy and tone. Overall, the AI systems' responses were considered appropriate, respectful of ethics and privacy, and useful in the clinical context. The article emphasizes the importance of understanding the reliability and precision of responses provided by AI systems in the clinical field. Although these systems offer high-quality responses, there is significant variability in their performance. Healthcare professionals must be aware of these differences and use such tools cautiously. AI can provide support in some aspects of care but cannot replace genuine human empathy and understanding. Integrating AI into clinical practice presents potential but also challenges, particularly the possibility of providing incorrect information. The AI systems demonstrate the ability to provide useful advice on clinical and psychological issues, but their use requires caution. It is crucial to distinguish the benefits of AI for patients from the challenges it presents for healthcare professionals. As AI technology continues to evolve, it is essential that its integration into the clinical field is accompanied by continuous research and evaluations, to ensure safe and effective use in the healthcare sector.

Unraveling the Natural History of Good’s Syndrome: A Progressive Adult Combined Immunodeficiency

Good's syndrome (GS) is a rare immune deficiency described almost 6 decades ago. Despite numerous published individual case reports and data collected in cross-sectional studies of small cohorts, the natural history and long-term outcomes of this disease remain unknown. We aimed to determine the clinical and laboratory evolution of 8 adults diagnosed with GS and consecutively evaluated between 1983 and2023. In this prospective, longitudinal cohort study, newly diagnosed patients with GS were followed through repeated measures of clinical, immune, and hematologic changes, as well as targeted genetic screening. All patients reported a healthy childhood and adolescence with symptom onset during the third or fourth decade of life. All presented to our center with recurrent bacterial sinopulmonary infections, thymoma, hypogammaglobulinemia, and absence of B cells. The median age of GS diagnosis was 57 years. During follow-up, immunoglobin replacement therapy effectively minimized sinopulmonary infections. However, the majority experienced severe and systemic viral or fungal infections, 3 developed basal cell carcinomas, and 5 had progressive bronchiectasis and persistent splenomegaly. The most notable clinical feature was opportunistic infections and invitro evidence of cellular immune deficiency, which resulted in the death of 2 individuals. We also report a statistically significant, multidecade progressive decline in lymphocytes, platelets, hemoglobin, and red blood cells in our cohort, suggesting gradual bone marrow failure. Knowledge of the unique phenotype and temporal evolution of GS has allowed us to develop a more comprehensive diagnostic framework. It can be investigated as part of broader research into disease pathophysiology.

In-depth blood immune profiling of Good syndrome patients.

Good 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). Here, 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). All 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. Our 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.

Good's syndrome: brief overview of an enigmatic immune deficiency.

Good's syndrome, an infrequent adult-onset immunodeficiency is characterized by the triad of thymoma, hypogammaglobulinemia, and increased susceptibility to recurrent infections. The clinical presentation is highly variable, with a spectrum ranging from recurrent bacterial and opportunistic infections to concomitant autoimmune diseases and, sometimes malignant pathologies. Due to heterogeneous clinical phenotypes and the lack of adequate diagnostic criteria, its recognition is often challenging, even delaying it by years. It is one of the most unusual, less studied form of the immune deficiency syndromes with a still unknown pathophysiology. It was initially considered a thymoma-associated variant of primary antibody deficiencies with a reduced or absent number of mature B cells, but it later emerged that significant defects of T cell-mediated immune functions are the underlying cause of opportunistic infections. On the basis of current evidence, Good's syndrome is evaluated as a distinct acquired form of combined immunodeficiency states and classified as a phenocopy of primary immunodeficiency diseases. Epigenetic and acquired genetic factors can play an ultimate role in its evolution.

Immunocytometric analysis of patients with thymic epithelial tumors revealed that COVID-19 vaccine booster strongly enhanced the immune response.

Thymic epithelial tumors (TETs) are rare malignancies with heterogeneous clinical manifestations. The high frequency of autoimmune paraneoplastic disorders observed in such patients requires caution when using COVID-19 vaccines. Furthermore, TETs are often associated with severe immunodeficiency, making it difficult to predict vaccine immunization. Therefore, we aimed to evaluate immune response to COVID-19 vaccine in patients with TETs. We conducted a prospective study enrolling patients who underwent the SARS-Cov-2 mRNA full vaccine cycle (two doses plus a booster after 6 months of BNT162b2). All patients were enrolled before receiving 1st vaccine dose and were followed over the vaccination cycle for up to 6 months after the booster dose to i) assess humoral and cellular responses, ii) define biomarkers predictive of effective immunization, and iii) evaluate the safety of the vaccine. At the end of the full vaccine cycle, 27 (61.4%) patients developed humoral and 38 (86.4%) cellular responses (IFN γ release by stimulated cells) and showed an increase in activated TH1 and TH17 cells, particularly significant after the booster dose. The number of B and T lymphocytes at baseline was predictive of humoral and cellular responses, respectively. Patients with no evidence of tumor lesions had a higher probability of achieving a humoral response than those with evidence of the disease. Furthermore, the percentage of patients with immune-related disorders (75%), particularly Good's syndrome (47.7%) and myasthenia gravis (29.5%), did not change over the entire vaccine cycle. Overall, 19 of the 44 enrolled patients (43.2%) had COVID-19 during the observation period; none required hospitalization or oxygen support, and no fatalities were observed. SARS-Cov-2 mRNA vaccine determines the immune responses in patients with TET, particularly after the booster dose, and in patients with no evidence of tumor lesions. Preliminary analysis of B and T lymphocytes may help identify patients who have a lower probability of achieving effective humoral and cellular responses and thus may need passive immunization. The vaccine prevented severe COVID-19 infection and is safe.

Impaired Seroconversion After Severe Acute Respiratory Syndrome Coronavirus 2 mRNA Vaccine in Patients With Thymic Epithelial Tumors

IntroductionThymic epithelial tumors (TETs) are rare malignancies associated with dysregulation of the immune system and humoral- and cell-mediated immunity abnormalities. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccine is effective in preventing coronavirus disease 2019 morbidity and mortality. The aim of this study was to evaluate the seroconversion in patients with TET after two doses of mRNA vaccine. MethodsThis is a prospective study in which consecutive patients with TET were enrolled before receiving the first dose of SARS-CoV-2 mRNA vaccine (BNT162b2 by Pfizer-BioNTech). SARS-CoV-2 spike-binding immunoglobulin (Ig)G antibody serologic levels were analyzed at different time points, including before first vaccine dose (T0), 1 month after the second dose (T2), and 3 months after the second dose (T3). ResultsOverall, 39 patients were included in the analysis. All patients had negative antibody titer results at T0. There were 19 patients (48.7%) in the follow-up with no residual tumor lesion/s (referred as no evidence of disease), and 20 (51.3%) had evidence of disease (ED) and were receiving systemic treatment. Dysregulations of the immune system were diagnosed in 29 patients (74.4%) with Good syndrome (GS) being the most frequent immune disorder (48.7%). At univariate analysis, lack of seroconversion at T2 was significantly associated with ED (p < 0.001) and with GS (p = 0.043). A significant association with impaired seroconversion was confirmed at multivariate analysis for ED (p = 0.00101) but not for GS (p = 0.625). ConclusionsOur data revealed that patients with TET with ED had substantially higher probability of impaired seroconversion after SARS-CoV-2 mRNA vaccine as compared with patients with no evidence of disease.

Immunological signature of patients with thymic epithelial tumors and Good syndrome: Correlation with clinical outcome.

e20648 Background: Thymic epithelial tumors (TETs) are extremely rare and heterogenous neoplasms, associated with immune dysregulation. Recognized prognostic factors are TNM stage and the Masaoka-Koga classification. To the best of our knowledge, no study has been conducted to investigate the correlation between immunophenotype, level of cytokines, chemochines and clinical outcome in TETs patients. The aim of this study was to evaluate the correlation of immunological signature and long-term outcome in patients with TETs and Good Syndrome (GS). Methods: From May 2019 to October 2022, consecutive patients with TETs and GS, referred to the Rare Tumors Coordinating Center of Campania Region (CRCTR) of Federico II of Naples, were enrolled. The immunophenotype of monocytes, neutrophils, eosinophils, CD4+ T cells, CD8 + T cells, B-cells, NK cells and NKT-cells, T regulatory cells, and the evaluation of serum levels of cytokines, chemokines and growth factors were assessed using the 8-color immunophenotyping kit, Treg detection kit and pre-formed Kits by Bioplex multiplex, respectively. D’Agostino-Pearson normality test was used to evaluate whether the continuous data were normally distributed, and a two-tailed t-test for independent samples was used. Overall survival (OS) analysis was performed generating Kaplan-Meier curves and Cox Univariate models for the considered categorical stratifications. p-values &lt; 0.05 were considered statistically significant. Results: A total of 24 consecutive TETs patients were included in the study: 13 (54.17%) patients were male and 11 (48.83%) were female, with a median age of 54.96 ± 9.6 years. Tumor histology included 20 thymoma, and 4 thymic carcinoma. Autoimmune diseases were found in 13 patients all of whom had thymoma. At the time of this analysis, 5 (20.83%) patients had no evidence of disease (NED) by imaging and were in follow-up, 17 (70.83%) patients were still alive. The analysis of leucocytes did not show statistically significant association with clinical outcome of TETs patients. On the contrary, a statistically significant correlation between serum concentration of IL-6 and OS was found with lower levels of IL-6 associated with poorer prognosis (HR: 9.654; p = 0.016). In addition, we found a statistically significant reduction of IL-2 (p = 0.04), IL-15 (p = 0.048), IL-5 (p = 0.03) and VEGF (p = 0.01) serum levels in patients with evidence of disease, as compared to NED patients. Conclusions: Overall, these findings suggest that measurement of IL-6 levels may be a useful parameter for identifying TETs patients with GS who have more aggressive diseases. Our preliminary data may be useful in the clinical management of this complex disease. Further studies are needed to better understand the pathophysiology and clinical implications of immunophenotype alterations in TETs patients.

Good's Syndrome: Thymoma with Acquired Immunodeficiency.

Good's Syndrome: Thymoma with Acquired Immunodeficiency.

Oral Lichen Planus in Patients With Good's Syndrome: A Literature Review.

Good's syndrome is defined as the association of a thymoma with an immune deficiency. Many patients with Good's syndrome also have oral lichen planus involvement, and some authors have even considered it to be one of the clinical signs of Good's syndrome. In the literature, to our knowledge, clinical forms of oral lichen planus associated with Good's syndrome have not been described. We therefore aimed to characterize the forms of oral lichen planus occurring in the context of Good's syndrome. To this end, we carried out a scoping review of the literature according to the Joanna Briggs Institute guide and included 17 articles on the theme of "the forms and clinical locations of oral lichen planus associated with Good's syndrome". A total of 17 articles were selected, and 19 patients with Good's syndrome including oral lichen planus were identified. Most of them were women aged 60 years with erosive oral lichen planus of the tongue and inner cheeks. The treatments used were thymectomy, to which immunoglobulin infusions were added in some cases. All these treatments resulted in improvement of the oral lichen planus in 70.6% of cases. The management of Good's syndrome allows the improvement of oral lichen. In patients over 50 years of age with acute erosive oral lichen planus refractory to conventional therapies, Good's syndrome should be investigated.

Good's Syndrome with Lichen Planus, HSV- Related Oral Ulcer, and Refractory Oral Candidiasis

Good's Syndrome with Lichen Planus, HSV- Related Oral Ulcer, and Refractory Oral Candidiasis

A Case of Good\'s Syndrome Presenting with Pulmonary Tuberculosis

Adult onset immunodeficiency associated with thymoma is a rare condition. The combination of hypogammaglobulinemia, reduced number of peripheral B and CD4+ T cells, along with thymoma constitutes Good's syndrome (GS). This immunodeficiency condition is often complicated with opportunistic infection with organisms, like bacteria (Haemophilus influenzae, Streptococcus pneumonia etc), viruses (Cytomegalovirus, Herpes simplex etc), fungi and protozoa. We present an unusual case of Good's syndrome with pulmonary tuberculosis (PTB). A 40-year-old man presented with sputum-positive PTB and was started on anti-tuberculosis treatment. Subsequently, he developed symptoms and findings consistent with thymoma and other components of Good's syndrome. Although patients of Good's syndrome are susceptible to various opportunistic infections, infection with Mycobacterium tuberculosis is uncommon. Evidence of recurrent infections or some opportunistic infection in a thymoma patient should trigger a suspicion of Good's syndrome.

Immunological signature of patients with thymic epithelial tumors and Good syndrome.

Thymic epithelial tumors (TETs) are frequently accompanied by Good Syndrome (GS), a rare immunodeficiency, characterized by hypogammaglobulinemia and peripheral B cell lymphopenia. TETs can be also associated to other immunological disorders, both immunodeficiency and autoimmunity. In this study, we enrolled TET patients with GS to address differences between patients with or without associated autoimmune diseases (AD). We analyzed the immunophenotype from peripheral blood of these patients focusing on selected immune cell subsets (CD4+T cells, CD8+T cells, T regulatory cells, NK cells, B-cells, monocytes, eosinophils, basophils, neutrophils) and serum levels of cytokines, chemokines and growth factors. We observed higher number of leucocytes, in particular lymphocytes, B lymphopenia and lower number of T regulatory cells in TET patients with associated AD compared to TET patients without AD. In the group of TET patients with AD, we also observed increased serum levels of IL-15, VEGF, IP-10, GM-CSF, IL-6, and MIP-1α. Thus, we identified considerable differences in the lymphocyte profiles of TET patients with and without ADs, in particular a reduction in the numbers of B lymphocytes and T-regulatory cells in the former, as well as differences in the serum levels of various immune modulators. Although the pathogenic mechanisms are still unclear, our results add new knowledge to better understand the disease, suggesting the need of surveilling the immunophenotype of TET patients to ameliorate their clinical management.

Immunological signature of patients with thymic epithelial tumors.

8589 Background: Thymic epithelial tumors (TETs) are complex diseases frequently associated with immune disorders, including Good Syndrome (GS). Etiopathogenesis of immune dysregulations in TETs patients is still not totally explained. The aim of this study was to evaluate differences in immune cell phenotype, as well as in the serum expression levels of a panel of cytokines, chemokines, and growth factors in patients with TETs and GS with or without autoimmune disorders (AD). Methods: From May 2019 to June 2020, consecutive patients with TETs and GS were recruited at Rare Tumors Coordinating Center of Campania Region (CRCTR – Naples, Italy). We analyzed the immunophenotype from peripheral blood focusing on selected immune cell subsets (monocytes, neutrophils, eosinophils, CD4+T cells, CD8+T cells, B-cells, NK cells and NKT- cells, T regulatory cells) processed for blood cell count and immunophenotyping, according to the 8-color immunophenotyping kit and Treg detection kit (CD4/CD25/CD127), and a panel of cytokines, chemokines, and growth factors from peripheral blood serum screened with pre-formed kits by Bioplex multiplex. D’Agostino-Pearson normality test was used to evaluate whether the continuous data were normally distributed, and a two-tailed t-test for independent samples was used. p-values &lt; 0.05 were considered statistically significant. Results: Overall, 29 patients were enrolled [17 (58.6%) with and 12 (41.4%) without AD]. Sixteen patients (55.2%) were female and 13 patients (44.8%) were male. Tumor histology included thymoma in all the patients with AD, whereas there were 10 cases of thymoma and 2 of thymic carcinoma in the group of patients without AD. The analysis of leucocytes by blood cell count showed a statistically significant higher number of leucocytes, ascribable to T lymphocytes (p = 0.023), B lymphopenia (p = 0.003) and decrease of T regulatory cells (p = 0.009) in TET patients with AD, as compared with TET patients without AD. Moreover, TET patients with AD showed significantly higher circulating levels of IL-15 (p = 0.032), VEGF (p = 0.007), IP-10 (p = 0.013), GM-CSF (p = 0.042), IL-6 (p = 0.031), and MIP-1α (p = 0.017) with respect to TET patients without AD. Conclusions: To our knowledge, this is the first report describing a profound alteration in B and T lymphocytes in TET patients associated with AD. The observed differences may be potentially important in the clinical management of this complex disease. Additional studies are needed to better understand the immunophenotypic alterations in TETs patients.

Prevalence of Anti-lymphocyte Antibodies in Patients with Good Syndrome and Partial RAG Deficiency

Good syndrome (GS) is a rare adult-onset progressive combined immunodeficiency typically characterized by thymoma, hypogammaglobulinemia and variable CD4+ lymphocytopenia. Of note, opportunistic infections and autoimmune complications have been increasingly recognized in these patients, implying underlying immune dysregulation. Autoantibody profiling, including the prevalence of antibodies targeting cytokines (associated with thymoma) and lymphocytes (associated with pathogenic lymphocytopenia) remains unclear.

Good's Syndrome: Time to Move on From Reviewing the Past.

For seven decades, the pathophysiology of Good’s syndrome (GS) has remained a mystery, with few attempts to solve it. Initially described as an association between hypogammaglobulinemia and thymoma, controversy exists whether this is a unique disease, or a subgroup of Common Variable Immune Deficiency (CVID). Recently, some distinguishing aspects of both syndromes have come to light reflecting fundamental differences in their underlying pathophysiology. GS and CVID differ in demographic features and immune phenotype. GS is found almost exclusively in adults and is characterized by a significantly reduced or absence of peripheral B cells. In CVID, which also occurs in children, most patients have normal or slightly reduced peripheral B cells, with a distinguishing feature of low memory B cells. Similarly, differences in T cell dysregulation and manifestations of hematologic cytopenias may further distinguish GS from CVID. Knowledge of the clinical phenotype of this rare adult immune deficiency stems from individual case reports, retrospective, and cross-sectional data on a few cohorts with a limited number of well characterized patients. The understanding of pathophysiology in GS is hampered by the incomplete and inconsistent reporting of clinical and laboratory data, with a limited knowledge of its natural history. In this mini review, we discuss current state of the art data and identify research gaps. In order to resolve controversies and fill in knowledge gaps, we propose a coordinated paradigm shift from incidence reporting to robust investigative studies, addressing mechanisms of disease. We hope this novel approach sets a clear direction to solve the current controversies.