A severe case of swimmer's itch in Victoria, Australia with bullous eruption.

Abstract: We describe a severe case of swimmer's itch in Victoria with widespread bullous eruption, which is a rare manifestation of this condition and presented a diagnostic challenge. This is the first case reported in Victoria, having been previously reported in more northern parts of Australia; with climate change trends, swimmer's itch is likely to become increasingly common in southern parts of the region.

Uropathogenic Escherichia coli infection: innate immune disorder, bladder damage, and Tailin Fang II.

Background: Uropathogenic Escherichia coli (UPEC) activates innate immune response upon invading the urinary tract, whereas UPEC can also enter bladder epithelial cells (BECs) through interactions with fusiform vesicles on cell surfaces and subsequently escape from the vesicles into the cytoplasm to establish intracellular bacterial communities, finally evading the host immune system and leading to recurrent urinary tract infection (RUTI). Tailin Fang II (TLF-II) is a Chinese herbal formulation composed of botanicals that has been clinically proven to be effective in treating urinary tract infection (UTI). However, the underlying therapeutic mechanisms remain poorly understood. Methods: Network pharmacology analysis of TLF-II was conducted. Female Balb/C mice were transurethrally inoculated with UPEC CFT073 strain to establish the UTI mouse model. Levofloxacin was used as a positive control. Mice were randomly divided into four groups: negative control, UTI, TLF-II, and levofloxacin. Histopathological changes in bladder tissues were assessed by evaluating the bladder organ index and performing hematoxylin-eosin staining. The bacterial load in the bladder tissue and urine sample of mice was quantified. Activation of the TLR4-NF-κB pathway was investigated through immunohistochemistry and western blotting. The urinary levels of interleukin (IL)-1ß and IL-6 and urine leukocyte counts were monitored. We also determined the protein expressions of markers associated with fusiform vesicles, Rab27b and Galectin-3, and levels of the phosphate transporter protein SLC20A1. Subsequently, the co-localization of Rab27b and SLC20A1 with CFT073 was examined using confocal fluorescence microscopy. Results: Data of network pharmacology analysis suggested that TLF-II could against UTI through multiple targets and pathways associated with innate immunity and inflammation. Additionally, TLF-II significantly attenuated UPEC-induced bladder injury and reduced the bladder bacterial load. Meanwhile, TLF-II inhibited the expression of TLR4 and NF-κB on BECs and decreased the urine levels of IL-1ß and IL-6 and urine leukocyte counts. TLF-II reduced SLC20A1 and Galectin-3 expressions and increased Rab27b expression. The co-localization of SLC20A1 and Rab27b with CFT073 was significantly reduced in the TLF-II group. Conclusion: Collectively, innate immunity and bacterial escape from fusiform vesicles play important roles in UPEC-induced bladder infections. Our findings suggest that TLF-II combats UPEC-induced bladder infections by effectively mitigating bladder inflammation and preventing bacterial escape from fusiform vesicles into the cytoplasm. The findings suggest that TLF-II is a promising option for treating UTI and reducing its recurrence.

No causal association between pneumoconiosis and three inflammatory immune diseases: a Mendelian randomization study.

Objectives: To investigate the causal relationships between pneumoconiosis and rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and gout. Methods: The random-effects inverse variance weighted (IVW) approach was utilized to explore the causal effects of the instrumental variables (IVs). Sensitivity analyses using the MR-Egger and weighted median (WM) methods were did to investigate horizontal pleiotropy. A leave-one-out analysis was used to avoid the bias resulting from single-nucleotide polymorphisms (SNPs). Results: There was no causal association between pneumoconiosis and SLE, RA or gout in the European population [OR = 1.01, 95% CI: 0.94-1.10, p = 0.74; OR = 1.00, 95% CI: 0.999-1.000, p = 0.50; OR = 1.00, 95% CI: 1.000-1.001, p = 0.55]. Causal relationships were also not found in pneumoconiosis due to asbestos and other mineral fibers and SLE, RA and gout [OR = 1.01, 95% CI: 0.96-1.07, p = 0.66; OR = 1.00, 95% CI: 1.00-1.00, p = 0.68; OR = 1.00, 95% CI: 1.00-1.00, p = 0.20]. Conclusion: Our study suggests that pneumoconiosis may have no causal relationship with the three inflammatory immune diseases.

Immune-mediated diseases are associated with a higher risk of ALS incidence: a prospective cohort study from the UK Biobank.

Objective: The occurrence of immune-mediated diseases (IMDs) in amyotrophic lateral sclerosis (ALS) patients is widely reported. However, whether IMDs and ALS is a simple coexistence or if there exists causal relationships between the two has been a subject of great interest to researchers. Methods: A total of 454,444 participants from the prospective cohort of UK Biobank were recruited to investigate the longitudinal association between IMDs and ALS. Previously any IMDs and organ specific IMDs were analyzed in relation to the following incident ALS by Cox-proportional hazard models. Subgroup analyses were performed to explore the covariates of these relationships. Results: After adjusting for potential covariates, the multivariate analysis showed that any IMDs were associated with an increased risk of ALS incidence (HR:1.42, 95%CI:1.03-1.94). IMDs of the endocrine-system and the intestinal-system were associated with increased risk of ALS incidence (endocrine-system IMDs: HR:3.01, 95%CI:1.49-6.06; intestinal system IMDs: HR:2.07, 95%CI: 1.14-3.77). Subgroup analyses revealed that immune burden, including IMD duration and the severity of inflammation had specific effects on the IMD-ALS association. In participants with IMD duration≥10 years or CRP≥1.3mg/L or females, previous IMDs increased the risk of incident ALS; however, in participants with IMD duration <10 years or CRP<1.3mg/L or males, IMDs had no effect on incident ALS. Interpretation: Our study provides evidence that previous any IMDs and endocrine-system and the intestinal-system specific IMDs are associated with an increased risk of developing ALS in females, but not in males.

[The association between baseline TPOAb and/or TgAb positivity and thyroid immune-related adverse events in patients with malignancies following treatment with immune checkpoint inhibitors].

Objective: To investigate the association between positive anti-thyroid peroxidase antibody (TPOAb) and/or anti-thyroglobulin antibody (TgAb) and the occurrence of thyroid immune-related adverse events (irAEs) in patients with malignant tumors who treated with immune checkpoint inhibitors (ICIs). Methods: A case-control study. A total of 116 patients with malignant tumor who received ICIs treatment and underwent thyroid function evaluation at Peking Union Medical College Hospital from January 2017 to April 2023 were enrolled retrospectively, including 77 males and 39 females, with a median age of (M(Q1, Q3)) 63.0 (55.0, 70.0) years. The patients were divided into the euthyroid group (n=58) and the thyroid irAEs group (n=58) according to whether thyroid irAEs occurred after ICIs treatment. The clinical characteristics and baseline anti-thyroid antibodies associated with the occurrence of thyroid irAEs after ICIs treatment in patients with malignant tumors were evaluated. Variables with statistical significance in univariate analysis were included in multivariate logistic regression model to analyze the risk factors for thyroid irAEs in patients with malignant tumors who received ICIs treatment. Results: In irAEs group, therewore 4 (3.4%) cases of clinical thyrotoxicosis, 23(19.8%) cases of subclinical thyrotoxicosis, 23 (19.8%) cases of clinical hypothyroidism, and 8(6.9%) cases of subclinical hypothyroidism. The positive rate of anti-thyroid antibodies at baseline in the thyrioid irAEs group was higher than that in the euthyroid group［16/58（27.6%）vs 3/58（5.2%），P=0.001］. After at least one course of ICIs treatment, the incidence of thyroid irAEs in patients with positive anti-thyroid antibodies at baseline was 84.2% (16/19), whereas it was 43.3% (42/97) in patients with negative anti-thyroid antibodies(P=0.001). Univariate logistic regression analysis showed that gender (OR=2.812, 95%CI:1.257-6.293), baseline thyroid autoantibodies were positive (OR=6.984, 95%CI: 1.909-25.547), baseline TgAb positivity (OR=8.909, 95%CI: 1.923-41.280), and baseline TPOAb positivity (OR=7.304, 95%CI: 1.555-34.308) were associated with thyroid irAEs (all P<0.05). Multivariate logistic regression analysis indicated that baseline TgAb positivity (OR=7.637, 95%CI: 1.617-36.072) was a risk factor for thyroid irAEs (P=0.01). Conclusions: The incidence of thyroid irAEs is higher in patients who are positive for baseline TPOAb and/or TgAb compared to those who are negative for TPOAb and TgAb. Patients with positive TgAb at baseline are at high risk of developing thyroid irAEs.

Association between the Prognostic Nutritional Index and the Occurrence of Immune-Related Adverse Events.

Immune-related adverse events (irAEs) affect all organs and are associated with various symptoms. The identification of biomarkers that can predict irAEs may be particularly clinically useful. This study aimed to investigate whether the prognostic nutritional index (PNI) before the initiation of immune checkpoint inhibitor (ICI) treatment can predict the occurrence of irAEs. We conducted a survey of 111 patients with cancer who were receiving ICI fixed-dose monotherapy at Saga University Hospital from the time each ICI became available until January 2020. We compared the PNI between the patients with and without irAE expression, established a cutoff value for PNI associated with the development of irAEs, and investigated the incidence of irAEs and progression-free survival (PFS) in groups divided by the cutoff value. Patients with irAEs had significantly higher PNI than did those without, and there was a significant association between PNI and irAEs after adjusting for potential factors (odds ratio, 1.12; 95% confidence interval, 1.03-1.21). In addition, PNI ≥44.2 was associated with a significantly higher incidence of irAEs (75.0% vs. 35.2%, p = 0.0001) and significantly longer PFS than PNI <44.2 (p = 0.025). In conclusion, pretreatment PNI may be associated with the risk of developing irAEs in patients with advanced recurrent solid tumors. When the PNI is ≥44.2, patient management is important for avoiding serious AEs because while the treatment may be effective, the occurrence of irAEs is a concern.

Mapping the functional impact of non-coding regulatory elements in primary T cells through single-cell CRISPR screens.

BACKGROUND: Drug targets with genetic evidence are expected to increase clinical success by at least twofold. Yet, translating disease-associated genetic variants into functional knowledge remains a fundamental challenge of drug discovery. A key issue is that the vast majority of complex disease associations cannot be cleanly mapped to a gene. Immune disease-associated variants are enriched within regulatory elements found in T-cell-specific open chromatin regions. RESULTS: To identify genes and molecular programs modulated by these regulatory elements, we develop a CRISPRi-based single-cell functional screening approach in primary human T cells. Our pipeline enables the interrogation of transcriptomic changes induced by the perturbation of regulatory elements at scale. We first optimize an efficient CRISPRi protocol in primary CD4+ T cells via CROPseq vectors. Subsequently, we perform a screen targeting 45 non-coding regulatory elements and 35 transcription start sites and profile approximately 250,000 T -cell single-cell transcriptomes. We develop a bespoke analytical pipeline for element-to-gene (E2G) mapping and demonstrate that our method can identify both previously annotated and novel E2G links. Lastly, we integrate genetic association data for immune-related traits and demonstrate how our platform can aid in the identification of effector genes for GWAS loci. CONCLUSIONS: We describe "primary T cell crisprQTL" - a scalable, single-cell functional genomics approach for mapping regulatory elements to genes in primary human T cells. We show how this framework can facilitate the interrogation of immune disease GWAS hits and propose that the combination of experimental and QTL-based techniques is likely to address the variant-to-function problem.

Novel premature termination codon in the FOXP3 gene as the cause of familial hydrops fetalis in males.

A 19-year-old, G1P0, pregnant person was referred at 20w2d gestation for evaluation due to non-immune hydrops fetalis (NIHF), which was confirmed at the time of evaluation. Amniocentesis was performed at 20 w4d, and FISH, karyotype, chromosomal microarray, and exome sequencing (ES) were ordered. Trio ES identified a novel hemizygous c.142 C > T (p.Arg48*; maternally inherited) variant in the FOXP3 gene, resulting in a premature termination codon and establishing the diagnosis of immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome. Intrauterine fetal demise (IUFD) was diagnosed at 21w3d. CVS was performed at 12w1d in a subsequent pregnancy (male fetus) and the known familial variant was identified. NIHF was identified at 18w1d. Ultrasound at 19w2d revealed IUFD. This is the first report of this variant in a diagnosis of IPEX syndrome, presenting with NIHF and male fetal demise. Genotype-phenotype correlations are not available in many cases of IPEX syndrome, as the same genotype can be present with variable severity in different individuals. Given the near identical presentations in this family, we anticipate a more severe phenotype with this variant. We propose a novel variant resulting in an early premature termination codon as an explanation for the severe presentation of IPEX syndrome in two successive fetuses in this family.

JAK/STAT defects and immune dysregulation, and guiding therapeutic choices.

Inborn errors of immunity (IEIs) encompass a diverse spectrum of genetic disorders that disrupt the intricate mechanisms of the immune system, leading to a variety of clinical manifestations. Traditionally associated with an increased susceptibility to recurrent infections, IEIs have unveiled a broader clinical landscape, encompassing immune dysregulation disorders characterized by autoimmunity, severe allergy, lymphoproliferation, and even malignancy. This review delves into the intricate interplay between IEIs and the JAK-STAT signaling pathway, a critical regulator of immune homeostasis. Mutations within this pathway can lead to a wide array of clinical presentations, even within the same gene. This heterogeneity poses a significant challenge, necessitating individually tailored therapeutic approaches to effectively manage the diverse manifestations of these disorders. Additionally, JAK-STAT pathway defects can lead to simultaneous susceptibility to both infection and immune dysregulation. JAK inhibitors, with their ability to suppress JAK-STAT signaling, have emerged as powerful tools in controlling immune dysregulation. However, questions remain regarding the optimal selection and dosing regimens for each specific condition. Hematopoietic stem cell transplantation (HSCT) holds promise as a curative therapy for many JAK-STAT pathway disorders, but this procedure carries significant risks. The use of JAK inhibitors as a bridge to HSCT has been proposed as a potential strategy to mitigate these risks.

Enrichment of Immune Dysregulation Disorders in Adult Patients with Human Inborn Errors of Immunity.

Human inborn errors of immunity (IEI) comprise a group of diseases resulting from molecular variants that compromise innate and adaptive immunity. Clinical features of IEI patients are dominated by susceptibility to a spectrum of infectious diseases, as well as autoimmune, autoinflammatory, allergic, and malignant phenotypes that usually appear in childhood, which is when the diagnosis is typically made. However, some IEI patients are identified in adulthood due to symptomatic delay of the disease or other reasons that prevent the request for a molecular study. The application of next-generation sequencing (NGS) as a diagnostic technique has given rise to an ever-increasing identification of IEI-monogenic causes, thus improving the diagnostic yield and facilitating the possibility of personalized treatment. This work was a retrospective study of 173 adults with IEI suspicion that were sequenced between 2005 and 2023. Sanger, targeted gene-panel, and whole exome sequencing were used for molecular diagnosis. Disease-causing variants were identified in 44 of 173 (25.43%) patients. The clinical phenotype of these 44 patients was mostly related to infection susceptibility (63.64%). An enrichment of immune dysregulation diseases was found when cohorts with molecular diagnosis were compared to those without. Immune dysregulation disorders, group 4 from the International Union of Immunological Societies Expert Committee (IUIS), were the most prevalent among these adult patients. Immune dysregulation as a new item in the Jeffrey Model Foundation warning signs for adults significantly increases the sensitivity for the identification of patients with an IEI-producing molecular defect.

[Clinical features and genetic analysis of three patients with Immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome due to variants of FOXP3 gene].

OBJECTIVE: To analyze the clinical characteristics of three patients with Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome. METHODS: Three patients with IPEX syndrome diagnosed at the Children's Hospital of Fudan University from January 24, 2013 to July 29, 2019 were selected as the study subjects. Their clinical features, laboratory investigations and results of genetic testing were summarized. Treatment and prognosis were also explored. RESULTS: All of the three children had developed the disorder during infancy. One child had initial features including diabetes and diabetic ketoacidosis, whilst the other two had initiated by diarrhea. All patients had gastrointestinal involvement, and one was diagnosed as very early onset inflammatory bowel disease by colonoscopy and biopsy. Two children also had endocrine glands involvement. One child had manifested type 1 diabetes and positivity for thyroglobulin and thyroid peroxidase antibodies, though his thyroid function had remained normal. Another one had hypothyroidism and was treated by levothyroxine. Genetic testing revealed that all children had harbored missense variants of the FOXP3 gene, including c.1222G>A (p.V408M), c.767T>C (p.M256T) and c.1021A>G (p.T341A). The clinical symptoms of one patient were alleviated following allogeneic hematopoietic stem cell transplantation. One patient was stable after treatment with infliximab plus insulin, and one child had died of refractory septic shock and multiple organ dysfunction syndrome at 3 months old. CONCLUSION: FOXP3 gene variant-associated IPEX syndrome may have very early onset and diverse clinical manifestations. For male patients with infantile onset chronic diarrhea, multiple endocrine or multiple system involvement, genetic testing is recommended, which may facilitate early diagnosis, treatment and genetic counseling.

Gut microbiome for predicting immune checkpoint blockade-associated adverse events.

BACKGROUND: The impact of the gut microbiome on the initiation and intensity of immune-related adverse events (irAEs) prompted by immune checkpoint inhibitors (ICIs) is widely acknowledged. Nevertheless, there is inconsistency in the gut microbial associations with irAEs reported across various studies. METHODS: We performed a comprehensive analysis leveraging a dataset that included published microbiome data (n = 317) and in-house generated data from 16S rRNA and shotgun metagenome samples of irAEs (n = 115). We utilized a machine learning-based approach, specifically the Random Forest (RF) algorithm, to construct a microbiome-based classifier capable of distinguishing between non-irAEs and irAEs. Additionally, we conducted a comprehensive analysis, integrating transcriptome and metagenome profiling, to explore potential underlying mechanisms. RESULTS: We identified specific microbial species capable of distinguishing between patients experiencing irAEs and non-irAEs. The RF classifier, developed using 14 microbial features, demonstrated robust discriminatory power between non-irAEs and irAEs (AUC = 0.88). Moreover, the predictive score from our classifier exhibited significant discriminative capability for identifying non-irAEs in two independent cohorts. Our functional analysis revealed that the altered microbiome in non-irAEs was characterized by an increased menaquinone biosynthesis, accompanied by elevated expression of rate-limiting enzymes menH and menC. Targeted metabolomics analysis further highlighted a notably higher abundance of menaquinone in the serum of patients who did not develop irAEs compared to the irAEs group. CONCLUSIONS: Our study underscores the potential of microbial biomarkers for predicting the onset of irAEs and highlights menaquinone, a metabolite derived from the microbiome community, as a possible selective therapeutic agent for modulating the occurrence of irAEs.

The diagnostic role of the systemic inflammation index in patients with immunological diseases: a systematic review and meta-analysis.

The identification of novel, easily measurable biomarkers of inflammation might enhance the diagnosis and management of immunological diseases (IDs). We conducted a systematic review and meta-analysis to investigate an emerging biomarker derived from the full blood count, the systemic inflammation index (SII), in patients with IDs and healthy controls. We searched Scopus, PubMed, and Web of Science from inception to 12 December 2023 for relevant articles and evaluated the risk of bias and the certainty of evidence using the Joanna Briggs Checklist and the Grades of Recommendation, Assessment, Development, and Evaluation Working Group system, respectively. In 16 eligible studies, patients with IDs had a significantly higher SII when compared to controls (standard mean difference, SMD = 1.08, 95% CI 0.75 to 1.41, p < 0.001; I2 = 96.2%, p < 0.001; moderate certainty of evidence). The pooled area under the curve (AUC) for diagnostic accuracy was 0.85 (95% CI 0.82-0.88). In subgroup analysis, the effect size was significant across different types of ID, barring systemic lupus erythematosus (p = 0.20). In further analyses, the SII was significantly higher in ID patients with active disease vs. those in remission (SMD = 0.81, 95% CI 0.34-1.27, p < 0.001; I2 = 93.6%, p < 0.001; moderate certainty of evidence). The pooled AUC was 0.74 (95% CI 0.70-0.78). Our study suggests that the SII can effectively discriminate between subjects with and without IDs and between ID patients with and without active disease. Prospective studies are warranted to determine whether the SII can enhance the diagnosis of IDs in routine practice. (PROSPERO registration number: CRD42023493142).

Oat protein isolate-Pleurotus ostreatus ß-glucan conjugate nanoparticles bound to ß-carotene effectively alleviate immunosuppression by regulating gut microbiota.

Individuals with immune disorders cannot establish an adequate defense to pathogens, leading to gut microbiota dysbiosis. ß-Carotene can regulate immune response, but its bioavailability in vivo is very low. Herein, we developed a glycosylated oat protein-based nanoparticle to improve the application of ß-carotene for mitigating cyclophosphamide-induced immunosuppression and gut microbiota imbalance in mice. The results showed that the nanoparticles facilitated a conversion of ß-carotene to retinol or retinyl palmitate into the systemic circulation, leading to an increased bioavailability of ß-carotene. The encapsulated ß-carotene bolstered humoral immunity by elevating immunoglobulin levels, augmenting splenic T lymphocyte subpopulations, and increasing splenic cytokine concentrations in immunosuppressed mice. This effect was accompanied by the alleviation of pathological features observed in the spleen. In addition, the encapsulated ß-carotene restored the abnormal gut microbiota associated with immunosuppression, including Erysipelotrichaceae, Akkermansia, Bifidobacterium and Roseburia. This study suggested that nanoparticles loaded with ß-carotene have great potential for therapeutic intervention in human immune disorders by specifically targeting the gut microbiota.

Autoantibodies Against Dihydrolipoamide S-Acetyltransferase in Immune-Mediated Neuropathies.

BACKGROUND AND OBJECTIVES: This study aimed to identify disease-related autoantibodies in the serum of patients with immune-mediated neuropathies including chronic inflammatory demyelinating polyneuropathy (CIDP) and to investigate the clinical characteristics of patients with these antibodies. METHODS: Proteins extracted from mouse brain tissue were used to react with sera from patients with CIDP by western blotting (WB) to determine the presence of common bands. Positive bands were then identified by mass spectrometry and confirmed for reactivity with patient sera using enzyme-linked immunosorbent assay (ELISA) and WB. Reactivity was further confirmed by cell-based and tissue-based indirect immunofluorescence assays. The clinical characteristics of patients with candidate autoantibody-positive CIDP were analyzed, and their association with other neurologic diseases was also investigated. RESULTS: Screening of 78 CIDP patient sera by WB revealed a positive band around 60-70 kDa identified as dihydrolipoamide S-acetyltransferase (DLAT) by immunoprecipitation and mass spectrometry. Serum immunoglobulin G (IgG) and IgM antibodies' reactivity to recombinant DLAT was confirmed using ELISA and WB. A relatively high reactivity was observed in 29 of 160 (18%) patients with CIDP, followed by patients with sensory neuropathy (6/58, 10%) and patients with MS (2/47, 4%), but not in patients with Guillain-Barré syndrome (0/27), patients with hereditary neuropathy (0/40), and healthy controls (0/26). Both the cell-based and tissue-based assays confirmed reactivity in 26 of 33 patients with CIDP. Comparing the clinical characteristics of patients with CIDP with anti-DLAT antibodies (n = 29) with those of negative cases (n = 131), a higher percentage of patients had comorbid sensory ataxia (69% vs 37%), cranial nerve disorders (24% vs 9%), and malignancy (20% vs 5%). A high DLAT expression was observed in human autopsy dorsal root ganglia, confirming the reactivity of patient serum with mouse dorsal root ganglion cells. DISCUSSION: Reactivity to DLAT was confirmed in patient sera, mainly in patients with CIDP. DLAT is highly expressed in the dorsal root ganglion cells, and anti-DLAT antibody may serve as a biomarker for sensory-dominant neuropathies.

Evaluating the effectiveness of the Charlson Comorbidity Index in predicting immune checkpoint inhibitor-related adverse events.

Aims: Our study aimed to evaluate the effectiveness of the Charlson Comorbidity Index (CCI) in predicting immune-related adverse events (irAEs) in solid tumor patients receiving immunotherapy. Patients & methods/materials: The CCI score at the time of initiation of immunotherapy was calculated in 164 solid tumor patients receiving immunotherapy and the correlation between the CCI score and immune toxicity was evaluated. Results: A significant relationship was found between CCI score and irAEs in lung cancer and renal cell cancer patients. In malignant melanoma, no significant relationship was found between the CCI score and the occurrence of irAEs. Conclusion: We argue that CCI can be used to predict irAEs, but we believe that a specific comorbidity index that includes autoimmune diseases should be developed.

The aim of our study was to find a scale that can predict which patients are most likely to develop side effects of immunotherapy drugs, which work by stimulating the immune system. We evaluated whether the Charlson Comorbidity Index ­ a scale which already exists to predict the mortality of patients with serious conditions ­ was able to predict whether people with cancer experienced negative side effects from immunotherapy drugs. We found that it may be useful to predict these negative reactions in patients receiving immunotherapy to treat lung and kidney cancer. This means that the Charlson Comorbidity Index might be useful for patients with these types of cancers, to help predict whether they will experience negative side effects. This could help doctors and patients to take better precautions and be more prepared in the event that these side effects do occur.