Serum periostin: a sentinel for malignancy risk in kidney transplant recipients.

High preoparative levels of serum periostin are associated with poor prognosis in patients with hepatocellular carcinoma after hepatectomy

An effective serum biomarker may improve cholangiocarcinoma (CCA) management. Periostin (PN) has been demonstrated to be associated with aggressive CCA. The current study evaluated PN in blood serum for its diagnostic and prognostic potential in patients with CCA. Sera of 68 patients with CCA were collected prior to treatment, and PN levels were measured using an ELISA. Sera from 50 normal controls, 6 patients with benign liver diseases, 2 with hepatocellular carcinoma and 21 with breast cancer were analyzed. Immunohistochemistry of PN in CCA tissues was also investigated. The data were analyzed using the Mann-Whitney U test, Kaplan-Meier log rank tests, Cox proportional hazard regression models and Fisher's exact tests. The median serum PN level in patients with CCA was significantly increased compared with that in healthy controls, patients with benign liver diseases and patients with breast cancer (all P<0.05). Using an optimal threshold value of 94 ng/ml PN, the diagnostic values for CCA compared with other conditions demonstrated a sensitivity level of 0.38 [95% confidence interval (CI), 0.27–0.51], specificity of 0.90 (95% CI, 0.81–0.96), accuracy of 0.66 (95% CI, 0.58–0.74), positive predictive value of 0.76 (95% CI, 0.59–0.89) and negative predictive value of 0.63 (95% CI, 0.53–0.72) (P<0.001). Furthermore, PN stain in stromal fibroblasts in CCA tissues was associated with serum PN levels (P=0.001), and patients with CCA were classified as low (≤94 ng/ml) or high PN (>94 ng/ml) accordingly. High serum and tissue PN levels were significantly associated with reduced survival rate (P<0.001 and P=0.033, respectively). Serum PN was an independent prognostic factor with a hazard ratio of 3.197 (P=0.001). In conclusion, serum PN may be used to divide patients with intrahepatic CCA into high and low PN groups. Elevated serum PN may be utilized as a marker of poor prognosis in patients with CCA.

IntroductionEnd-stage renal disease (ESRD) treatment includes dialysis and kidney transplantation. Transplant rejection is a major barrier to transplant success. One of the markers mentioned in previous studies on renal function in patients with renal failure for various reasons is periostin (POSTN). The expression of POSTN correlates with interstitial fibrosis and reduced renal function. One of the limitations in this regard is the effect of oral lesions on the POSTN level. This study was conducted aimed to measure the relationship between salivary and serum POSTN and renal function in patients with a history of a kidney transplant, taking into account all the conditions affecting POSTN.MethodsIn this study, serum and saliva samples were taken from 23 transplant patients with normal function (NF) and 29 transplant patients with graft failure (GF). At least one year had passed since the transplant. Before sampling, a complete oral examination was performed. Salivary and serum POSTN was examined by ELISA. The results were analyzed by SPSS software.ResultsThe POSTN level in the serum of the NF group (191.00 ± 33.42) was higher than GF patients (178.71 ± 25.68), but the difference was not significant (P = 0.30). Salivary POSTN in NF patients (2.76 ± 0.35) was significantly higher than GF patients (2.44 ± 0.60) (P = 0.01).ConclusionsThe superiority of saliva as a diagnostic fluid includes ease of collection and storage, and non-invasiveness, all of which can lead to the replacement of blood with this bio-fluid. The significant results of salivary POSTN may be due to the lack of serum disturbing factors. Saliva is an ultra-filtered fluid from serum and therefore there are fewer proteins and polysaccharides attached to biomarkers in saliva and the accuracy of measuring these biomarkers in the saliva is more valuable than serum.

Periostin (POSTN) is a secreted γ-carboxyglutamic acid-containing protein expressed mainly in the periosteum in adult individuals. POSNT deficient mice develop periodontis and osteoporosis with decreased bone strength. The relationship between serum POSTN and bone metabolism and fracture risk in postmenopausal women is unknown. Serum POSTN was measured in 607 postmenopausal women (mean age 66.6 ± 8.4 y) from the Os des Femmes de Lyon cohort at the ninth annual follow-up visit (baseline visit of the current analysis). Nonvertebral and clinical vertebral incident fragility fractures were reported annually during 7 years. Areal bone mineral density (BMD; measured by dual energy X-ray absorptiometry) of the hip and bone markers (intact N-terminal propeptide of type I collagen, osteocalcin, and serum type I collagen C-telopeptide) were also measured. At baseline, serum POSTN did not correlate with age, bone markers, and BMD. After a median of 7 years of follow-up, 75 women sustained an incident clinical vertebral or nonvertebral fragility fracture. The proportion of women who had an incident fracture was significantly higher in women with levels of POSTN in the highest quartile than that of women in the three other quartiles (19.5% vs 10.1%, P = .018) after adjustment for age and prevalent fracture. The highest quartile of POSTN was associated with an increased risk of incident fracture with a relative risk (95% confidence interval) of 1.88 (1.1-3.2) after adjustment for age, prevalent fracture, and hip BMD T-score. Patients with both low hip BMD (T-score < -2.5) and high levels of POSTN (fourth quartile) had a relative risk of fracture of 7.1 (95% confidence interval 2.4-21.8) after adjustment for age. High serum POSTN levels are independently associated with increased fracture risk in postmenopausal women. These data suggest that serum POSTN could be useful to improve fracture risk assessment.

The aim of the study is to evaluate the relationship between serum periostin (POSTN), thymus and activation-regulated chemokine (TARC), and thymic stromal lymphopoietin (TSLP) levels and disease severity and atopy in children with atopic dermatitis. Sixty children with atopic dermatitis and 31 healthy controls were included in the study. The disease severity was measured by SCORAD scores. Serum POSTN, TARC, and TSLP levels were measured in all participants. The demographic data were recorded, and skin prick tests were performed to evaluate atopy in children with atopic dermatitis. Serum POSTN, TARC, and TSLP levels were higher in children with atopic dermatitis than in healthy children (p = 0.041, p = 0.034, and p < 0.001, respectively). Serum POSTN levels were higher with atopy than without atopy in children with atopic dermatitis (p = 0.047). There was a positive moderate correlation between POSTN and the age and symptom duration in children with atopic dermatitis (r = 0.343, p = 0.007, r = 0.484, and p < 0.0001, respectively). In receiver operating characteristics (ROC) analysis, the area under the curve (AUC) was 0.789 (95% CI (0.694 - 0.883), p < 0.0001) for TSLP and the AUC was 0.636 (95% CI (0.522 - 0.750), p = 0.034) for TARC to predict severe atopic dermatitis. Serum POSTN, TARC, and TSLP were higher in children with atopic dermatitis. Serum TARC and TSLP levels might be used as biomarkers to predict severe atopic dermatitis and serum POSTN to predict atopy and disease chronicity.

PN is a secreted cell adhesion protein critical for carcinogenesis. Elevated serum levels of PN have been implicated as playing an important role in different types of cancer, and a few reports suggest a potential role as a prognostic marker. We evaluated the prognostic significance of preoperative serum PN concentration in patients with BCa receiving curative surgery. Enzyme-Linked Immunosorbent Assay (ELISA) was performed to determine the preoperative serum PN level in 182 patients. The correlations between serum PN concentration with clinical pathological features and PN expression in primary tumor samples were analyzed. The prognostic impact of serum PN levels with all-cause and BCa-specific mortality was also investigated. Appropriate statistics were used. Elevated serum PN levels were significantly associated with patient age (p = 0.005), adjuvant systemic therapy (p = 0.04) and progesterone receptor (PgR) status (p = 0.02). No correlation between PN preoperative serum levels and other clinical-pathological parameters, including either the epithelial or the stromal PN expression of primary tumor or the combination of the two, was found. Similarly, no association between serum PN levels and either all-cause or BCa-specific mortality was found. However, subgroup analysis revealed a correlation between higher PN serum levels and all-cause mortality in patients with node-negative disease (p = 0.05) and in those with a low PgR expression (p = 0.03). Higher levels of serum PN were also found to correlate with BCa-specific mortality in the subgroup of patients who did not receive any adjuvant systemic therapy (p = 0.04). Our findings suggest that PN was detectable in the serum of early BCa patients before surgery and increased base-line serum levels predicted worse long-term survival outcomes in specific subgroups of patients.

Aims/Background Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by synovial inflammation, pannus formation, and neovascularization. Reliable biomarkers for monitoring RA activity are needed to optimize treatment strategies. Periostin (POSTN) and vascular endothelial growth factor (VEGF) contribute to tissue remodeling and angiogenesis in various diseases, but their combined role and clinical significance in RA remain underexplored. This study aimed to evaluate serum POSTN and VEGF levels in RA patients and their correlation with disease activity. Methods Serum levels of POSTN and VEGF were quantified using enzyme-linked immunosorbent assay (ELISA) in 86 RA patients, 36 osteoarthritis (OA) patients, and 40 healthy volunteers (HV) enrolled between January 2022 and December 2024 at Jinhua Municipal Central Hospital. RA patients were categorized into active (Disease Activity Score-28 [DAS28] >2.6) and stable (DAS28 ≤2.6) subgroups. Serum POSTN and VEGF levels were compared across the three study groups and between RA activity subgroups. Correlations between these biomarkers and clinical/laboratory parameters, including DAS28, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR), were analyzed. Results Serum POSTN and VEGF levels were significantly higher in RA patients [(125.21 ± 35.17) ng/mL, (106.45 ± 29.54) pg/mL] compared to OA patients [(98.41 ± 30.09) ng/mL, (82.28 ± 23.18) pg/mL] and healthy controls [(75.86 ± 22.81) ng/mL, (71.24 ± 11.72) pg/mL] (all p < 0.001). Furthermore, POSTN and VEGF levels in the active RA group [(144.68 ± 29.98) ng/mL, (121.75 ± 27.49) pg/mL] were significantly higher than those in the inactive group [(100.62 ± 24.23) ng/mL, (87.33 ± 19.12) pg/mL] (all p < 0.001). Spearman's or Pearson's correlation analyses revealed a positive correlation between POSTN and VEGF in RA patients (r = 0.708, p < 0.001). Serum POSTN levels were positively correlated with DAS28, CRP, and ESR (rDAS28 = 0.753, rCRP = 0.623, rESR = 0.437, p < 0.001) so was VEGF (rDAS28 = 0.720, rCRP = 0.433, rESR = 0.623, all p < 0.001). Conclusion POSTN and VEGF levels are elevated in RA patients, correlate with disease activity markers, and may serve as complementary biomarkers for assessing RA activity.

BackgroundBreast cancer (BCa) is the leading cause of cancer deaths among women. Reliable biomarkers for early diagnosis and metastasis prediction are essential to improve the prognosis of BCa. This study aimed to evaluate serum periostin (POSTN) as a novel biomarker complementing CA153 (carbohydrate antigen 153) and CEA (carcinoembryonic antigen) for BCa diagnosis and metastasis prediction.MethodsTo assess the potential of soluble POSTN as a circulating biomarker, 242 participants, including 173 patients with different stages of BCa and 69 healthy individuals, were enrolled in this study. Soluble POSTN, together with CA153 and CEA, were determined in serum by enzyme linked immunosorbent assay (ELISA) or electrochemiluminescence immunoassays.ResultsSerum POSTN levels in locoregional BCa patients were significantly higher than that in healthy controls. Receiver operating curve (ROC) analysis revealed that, to distinguish health controls from locoregional BCa, POSTN was observed with the highest AUC (area under curve) (AUCPOSTN = 0.72 [0.65 – 0.79], AUCCA153 = 0.57 [0.49 – 0.64], AUCCEA = 0.62 [0.55 – 0.69]), and both CA153 and CEA were observed with significantly improved AUCs by combination with POSTN (AUCPOSTN + CA153 = 0.74 [0.67 – 0.80], P < 0.001; AUCPOSTN + CEA = 0.77 [0.70 – 0.82], P < 0.001). Moreover, the performances of the POSTN were comparable with that of CA153 in predicting distant metastasis of BCa (AUCPOSTN = 0.78 [0.71 – 0.84], AUCCA153 = 0.82 [0.76 – 0.88]). Kaplan–Meier analysis indicated that elevated serum POSTN was associated with poor overall survival and progression-free survival.ConclusionsThis study suggested that soluble POSTN is a promising potential biomarker for diagnosis and metastasis prediction of BCa.

Predictors of severe COVID-19 in kidney transplant recipients in the different epidemic waves: Analysis of the Spanish Registry.

ObjectivesTo determine the average serum periostin level in children with asthma between 6 and 16 y of age, and to find out if the levels correlated with markers of eosinophilic inflammation, asthma control, and severity.MethodsChildren under follow-up at a tertiary care centre were enrolled. Children with conditions causing elevated serum periostin other than asthma, or history of systemic steroid use in the past 6 mo were excluded. Serum total IgE and periostin were estimated by ELISA.ResultsThe median (IQR) serum periostin level was 52.6 (45.4, 58.3) ng/mL. Levels did not vary with age, gender, duration of symptoms, positive family history, or history of exacerbations in the last 6 mo. There was no significant correlation with anthropometric parameters or their z scores, or markers of eosinophilic inflammation in blood including serum total IgE, eosinophil percentage or absolute eosinophil count. There was no difference in median periostin levels of children with different asthma symptom control or asthma severity.ConclusionsIn a group of 26 Indian children with physician-diagnosed asthma, serum periostin showed no significant correlation to markers of eosinophilic inflammation.

Serum periostin in smokers and never smokers with asthma

Introduction Risk-to-benefit ratio of upper extremity allotransplantation (UEA), a non-vital transplantation procedure, remains to be clarified, as concerns have been raised regarding infectious, metabolic and malignant complications of lifelong immunosuppression. The aim of this study was to provide a relevant assessment of the infectious risk in UEA recipients. Infectious complications in UEA recipients were analyzed and compared to that of kidney transplant (KT) recipients who have the lowest rate of infections among the different populations of solid organ transplant recipients. Patients and Methods Matched cohort study among UEA and KT recipients from the prospectively maintained “International Registry on Hand and Composite Tissue Transplantation” (IRHCTT) and the French “Données Informatisées et VAlidées en Transplantation” (DIVAT) database. All UEA recipients reported to the IRHCTT between 1998 and 2016 were matched with KT recipients (1:5), according to age (±5 years), sex, CMV serostatus of donor and recipient and (depleting or not depleting) induction. Incidence and characteristics of all infectious events reported to the databases at three posttransplant periods (0-6 months, 7-12 months, >12 months) were analyzed. Results and Discussion Sixty-one UEA recipients were matched with 305 KT recipients. Mean (±SD) follow-up of UEA and KT recipients was 2583±1876 and 2230±1792 days, respectively (p=0.16). Immunosuppression regimen at 3 months posttransplant was similar. The number of acute rejection episodes during follow-up was higher in UEA recipients than in KT recipients (1.3±1.6 vs 0.4±0.7, p<0.01). During follow-up, 30 (50.8%) UEA recipients presented a total of 61 infectious events while 129 (42.3%) KT recipients presented 243 infectious events. Incidence rate of infectious events was higher in UEA recipients than in KT recipients during the first 6 months posttransplant (3.27 vs 1.95 events/1000 transplant-days, p=0.01). Thereafter, incidence rates of infections did not significantly differ between UEA and KT recipients: 0.61 vs 0.45 events/1000 transplant-days (7th-12th month posttransplant, p=0.5) and 0.15 vs 0.21 events/1000 transplant-days (>12th month posttransplant, p=0.11), respectively. Distribution of sites of infections was significantly different: while mucocutaneous infections predominated among UEA recipients at each of the three posttransplant periods (representing 28.6%, 50% and 30% of infectious events, respectively), urinary tract infections (28.6%, 23.8% and 33.9%) and pneumonia (17.3%, 42.9% and 28.2%) predominated among KT recipients. Conclusion Incidence rate of infectious events is higher in UEA recipients than in KT recipients during the first 6 months posttransplant. After the first 6 months posttransplant, incidence of infections is low, at worst equivalent to the incidence observed in young KT recipients. Distribution of infectious syndromes suggests less severe infections in UEA than in KT recipients.

Background: The roles of periostin in patients with severe obstructive sleep apnea (OSA) remain unclear. Aims and objectives Serum periostin is a marker of type-2 inflammation and tends to increase in non-obese patients with asthma. Meanwhile‚ several in vitro studies suggest that impaired glycolipid metabolism, mechanical stress and hypoxia upregulate expression of periostin. Here‚ we aimed to clarify roles of periostin in patients with OSA‚ who are often obese but accompanied by these conditions. Methods: In patients diagnosed as having OSA‚ we examined associations between serum periostin levels and clinical indices‚ such as severity of OSA‚ body mass index (BMI)‚ and blood glucose and lipids. Assessments were done at baseline and after 3 months of continuous positive airway pressure (CPAP) treatment. Results: In 96 patients with OSA‚ serum periostin levels positively correlated with age and blood glucose and tended to correlate with BMI negatively (p = 0.055). When adjusted for BMI‚ severe OSA (apnea hypopnea index ≥ 30) tended to associate with elevated serum periostin (p = 0.07). Among 53 patients with severe OSA‚ patients with high serum periostin levels (highest quartile‚ ≥ 85ng⁄mL, n = 13) showed higher free fatty acid‚ fasting blood glucose and frequency of micro⁄overt albuminuria than those with severe OSA alone. In patients with severe OSA and high serum periostin‚ serum periostin and urinary albumin levels were significantly decreased after 3 months of CPAP treatment. Conclusions Serum periostin levels tend to increase in severe OSA‚ when adjusted for BMI. Elevated serum periostin in patients with severe OSA may indicate the risk of albuminuria‚ which could be reduced with CPAP treatment.

Coronavirus disease 2019 (COVID-19) has had a major effect on kidney and other solid organ transplant recipients.1 In addition to public health measures, improved access to testing, and therapeutic developments, vaccination has emerged as a key tool for controlling the ongoing pandemic. In December 2020, multiple regulatory agencies worldwide authorized the use of two mRNA vaccines for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and several other vaccine platforms are in advanced-stage clinical trials.2,3 Individuals who have received a transplanted kidney or other solid organ have been identified as high-risk populations and prioritized for vaccination in public health guidelines, but unfortunately have been excluded from major SARS-CoV-2 vaccine clinical trials.1,2 Thus, studies are urgently needed to characterize the safety, immunogenicity, and ultimately, efficacy of SARS-CoV-2 vaccines for such patients. Below, we provide an overview of SARS-CoV-2 vaccines and highlight key concepts that should be considered in evaluating their safety in solid organ transplant recipients. Despite the theoretical concerns described below, we emphasize that available evidence from studies demonstrates safety and efficacy in the general population. Because of the known substantial risks of COVID-19–associated morbidity and mortality in recipients of kidney and other solid organs, and the long track record of safety of other vaccinations in such recipients, we anticipate the benefits of selected SARS-CoV-2 vaccines will far outweigh risks of vaccination. Accordingly, current guidance from multiple professional organizations recommend vaccination for all eligible organ transplant recipients.2,4,5 Each vaccine platform has distinct safety considerations for kidney transplant recipients. Live (replication-competent) vaccines are generally contraindicated in immunocompromised individuals because of a risk of vaccine-acquired disease.6 The SARS-CoV-2 candidate vaccines that are furthest along in development do not contain replication-competent SARS-CoV-2 virus, and therefore do not carry risk of SARS-CoV-2 infection (Table 1). Table 1. - Major SARS-CoV-2 platforms in developmenta Vaccine Platform Vaccine Name (Manufacturer) Vehicle Phase of Development Adjuvant Safety and Efficacy in the General Population Specific Considerations for Kidney Transplant Recipients mRNA BNTb162b2 (Pfizer/BioNTech) mRNA encapsulated in lipid nanoparticles Authorized for emergency use in the United States and other countries Unadjuvanted, but lipid nanoparticles possess natural adjuvant activity7 95% efficacy in phase 3 trials.1 Anaphylaxis has been reported. Avoid in patients with a known allergy to a vaccine component (e.g., polyethylene glycol). Close monitoring after administration for patients with a history of anaphylaxis to any food or drug.3 Does not contain live virus. No evidence of vaccine-induced off-target immune responses in large phase 3 clinical trials.2,3 mRNA-1273 (Moderna) Replication-defective viral vectors AZD122 (Oxford/AstraZeneca) Human-chimpanzee adenovirus (ChAdOx1) Phase 3 Unadjuvanted 70%–90% efficacy depending on dose in phase 3 trials.8 Transverse myelitis reported.8 Removal of genes necessary for replication reduces risk of vaccine-associated AdV disease.9 Theoretical risk of emergence of new AdV type with replicative potential through homologous recombination, although this has never been demonstrated to occur with AdV-vectored vaccines.9 JNJ78436735/Ad26.COV2.S (Janssen) Human adenovirus (Ad26) Phase 3 Unadjuvanted Unknown Convidecia (Ad5-nCov) Human adenovirus (Ad5) Approved for limited use in China Unadjuvanted Unknown Sputnik V (Gamaleya) Human adenovirus (Ad5 and Ad26 in consecutive doses) Early use in Russia, Belarus, and Argentina Unadjuvanted Unknown Protein subunit NVX-CoV2373 (Novavax) Recombinant spike glycoprotein Phase 3 Matrix-M1 system plus an additional, unnamed adjuvant Unknown Does not contain live virus. Matrix-M1 contains the same QS21 saponin as the AS01B adjuvant system contained in the recombinant varicella zoster vaccine.7 SARS-CoV-2 recombinant protein formulation (GSK/Sanofi) Recombinant spike protein Phase 2 AS03 adjuvant Unknown High incidence of anti-HLA antibodies in KTR vaccinated with AS03-adjuvanted influenza vaccines, but no association between AS03 exposure and rejection.3,10 EpiVacCorona (Vector Institute) Peptide epitope Early use in Russia Unknown Limited data available Whole-inactivated (killed) BBIBP-CoV (Sinopharm) CoronaVac (SinoVac) Whole-inactivated SARS-CoV-2 viral particles Limited use in China and other countries Unknown Unknown Does not contain live virus. Limited data available in peer-reviewed literature. GSK, GlaskoSmithKline; KTR, kidney transplant recipients.aDoes not include all candidate vaccines or platforms under investigation; limited to platforms in advanced stages of clinical development or authorized for use as of December 31, 2020. However, viral vector–based vaccines that incorporate viruses other than SARS-CoV-2 are in advanced-phase studies, including adenovirus (AdV) vector–based vaccines that have been licensed in Europe. These vaccines consist of intact virions that are engineered to include the gene encoding the SARS-CoV-2 spike protein, a technique that leverages the viral vector's ability to efficiently infect cells and enhances spike gene delivery. Vaccines that use viral vectors contain either replication-deficient or replication-competent viruses (Table 1). The majority of viral-vectored vaccines in the most advanced phases of development have been rendered replication-deficient through deletion of genes essential for replication.8 By limiting vector replication, the potential for vaccine-associated AdV disease is greatly diminished. There are, however, theoretical mechanisms by which replication-deficient viral vector–based vaccines could become replication competent and cause disease, especially in immunocompromised individuals. For example, in cells concurrently infected with two different AdVes, homologous recombination of genetic elements could occur and result in the emergence of new, pathogenic, replication-competent AdV types.9 This has been observed in patients with advanced HIV disease during natural AdV infections, and is theoretically possible with AdV vector–based vaccines in patients who are immunocompromised with a concurrent wild-type AdV infection.9 Although infrequent, severe AdV infections, including allograft nephritis, can occur in kidney transplant recipients during natural infection.9 Notably, vaccine-associated AdV disease has not been reported, albeit there is little experience in immunocompromised populations. It should be emphasized that, despite the theoretical concerns with replication-deficient viral vector–based vaccines, immunosuppression is not considered a contraindication to their use.11 Replication-competent viral-vectored vaccines carry a greater risk of vaccine-derived vector infection in patients who are immunocompromised and should only be administered under carefully controlled circumstances (specifically, clinical trials). Other vaccine candidates that are in advanced stages of development, including mRNA, protein subunit, or whole virus–inactivated SARS-CoV-2 vaccines, do not contain intact virus and thus do not carry a risk of vaccine-associated infection.3 Induction of generalized systemic inflammation by either the vaccine antigen or an associated adjuvant, or by more specific cellular and humoral crossreactivity between vaccine epitopes and allograft antigens, theoretically could promote undesired allograft-directed immune responses. AdV vectors elicit potent innate immune responses through complement activation and induce a diverse cytokine repertoire.10 Although this phenomenon is most prominent at the site of AdV-vector inoculation, systemic inflammation could promote vaccine-associated allograft rejection. Concern for autoimmunity related to the SARS-CoV-2 vaccine on the basis of a modified chimpanzee AdV vector (ChAdOx1) arose after two vaccine recipients developed transverse myelitis, although the possibility of an unrecognized preexisting demyelinating condition has raised questions about the significance of one of these events.8In vitro reactivity between spike protein antibodies and human collagen has been demonstrated, but molecular mimicry has not been identified as a primary mechanism of kidney injury in COVID-19.12 Available data suggest acute allograft rejection is uncommon during COVID-19, despite frequent reduction in immunosuppression as a therapeutic strategy.1 In the absence of an observed association between natural SARS-CoV-2 infection and acute allograft rejection in kidney transplant recipients, it is unlikely that vaccine antigens would precipitate clinically significant immune responses to renal allografts. In general, adjuvants used to enhance vaccine immunogenicity also elicit nonspecific inflammatory responses, and thus have the potential to induce acute allograft rejection. Concern about adjuvant safety in organ transplant recipients arose from observations of an unusually high incidence of anti-HLA antibodies in kidney transplant recipients who received the 2009 influenza A(H1Na1)pdm09 vaccine, which contained the squalene-based AS03 adjuvant system.6,7 However, only a fraction of these anti-HLA antibodies were donor specific, and a subsequent investigation of >10,000 solid organ transplant recipients found no definitive association between the AS03 adjuvant system and acute allograft rejection.6 The AS01B adjuvant used in the recombinant varicella zoster virus vaccine contains a combination of monophosphoryl lipids and QS21, a saponin.13 This adjuvant induces a potent innate immune response and associated concerns for precipitating acute allograft rejection in kidney transplant recipients. Several recombinant spike protein SARS-CoV-2 vaccines contain adjuvants, such as AS03 and the novel Matrix M1 adjuvant, which contains the same QS21 saponin found in the recombinant varicella zoster vaccine.3 Viral-vectored and mRNA vaccines do not generally contain adjuvants, although lipid nanoparticle delivery devices used in the mRNA vaccines have natural adjuvant activity.13 Postmarketing surveillance will be essential to assess any potential association between SARS-CoV-2 vaccine components and acute allograft rejection. In the interim, theoretical concerns associated with any vaccine must be weighed against the benefits of preventing or mitigating the severity of a life-threatening infection in a vulnerable population. We emphasize that a broad range of vaccines have a substantial track record of safety in kidney and other solid organ transplant recipients. Furthermore, no definitive association between any vaccine or adjuvant and allograft rejection has been identified to date.2,6 Immunosuppression in kidney transplant recipients is anticipated to reduce the immunogenicity of SARS-CoV-2 vaccines, and immunogenicity may vary by vaccine platform. Available data across a broad range of vaccines in solid organ transplant recipients suggest they have relative humoral response rates that are approximately 50%–70% of those seen in nontransplant populations.6,7 Patients with ESRD may have more a robust response to vaccines before rather than after kidney transplant,6 and when possible, SARS-CoV-2 vaccines should be given before transplantation.2 In the post-transplant setting, age >65 years, more recent transplantation, use of mycophenolate and mammalian target of rapamycin inhibitors, and lower graft function are associated with decreased serologic responses to influenza vaccines.6,7 Despite the effects of lymphocyte-depleting immunosuppression in the early period after transplant or treatment for rejection, the benefits of even modest SARS-CoV-2 protection might outweigh the risk of delaying immunization during a pandemic.2 In general, vaccines are not recommended immediately post-transplant due to a presumed decrease in immunogenicity after recent high-level immunosuppression. Expert opinion advises that delaying SARS-CoV-2 vaccination of vaccine-naive transplant recipients until 3 months after transplant or receipt of T cell or B cell ablative therapies may be appropriate; for patients who received a first dose before transplant, administration of the second dose should be delayed until at least 4 weeks post-transplant.2 Higher doses, booster doses, adjuvants, and intradermal delivery have all been used with variable success to improve immunogenicity of commonly administered vaccines in solid organ transplant recipients.6,7 If immunogenicity of standard regimens in kidney transplant recipients is suboptimal, these alternative approaches should be considered. The diversity of vaccine platforms and phased vaccine allocation present unique challenges for assessing the safety, immunogenicity, and efficacy of SARS-CoV-2 vaccination in kidney transplant recipients. Surveillance for adverse events related to each specific formulation through prospective multicenter registries of vaccinated solid organ transplant recipients is one potential approach to assessing safety, especially given that large population-specific studies of kidney transplant recipients may not be feasible. Prospective clinical trials should directly compare different SARS-CoV-2 vaccine platforms, assess the magnitude and durability of humoral and cellular responses, and utilize the same functional laboratory immunogenicity assays as the vaccine trials to facilitate direct comparisons between transplant recipients and general populations. It is hoped these investigations will identify relevant differences among the various vaccine platforms to guide future studies of alternative vaccination strategies, if warranted. Because immunosuppression may increase SARS-CoV-2 viral load and prolong the duration of SARS-CoV-2 viral shedding and transmissibility, studies to monitor both symptomatic and asymptomatic infection in vaccinated kidney transplant recipients—with quantitation of viral loads, viral culture, or both—would complement studies of safety and immunogenicity. Large prospective studies of vaccine efficacy in kidney transplant recipients that include a placebo arm are likely not feasible and may not be ethically appropriate, depending on the final results of ongoing phase 3 studies. Case-control trials of kidney transplant recipients with COVID-19 that examine the effect of prior vaccination on disease severity, viral load, and duration of viral persistence, although less definitive, may offer a more practical approach. SARS-CoV-2 vaccines have significant potential to reduce COVID-19–associated morbidity and mortality among recipients of solid organ transplants, including kidney transplants. Because transplant recipients' responses to vaccines may be suboptimal, continued emphasis on nonvaccine preventive measures—use of face covers, hand hygiene, and physical distancing—will be needed, even after vaccination.2 Although the vaccines' ability to disrupt viral transmission in either immunocompetent or immunocompromised individuals is not yet established, vaccination of caregivers and close contacts of kidney transplant recipients, recommended for influenza vaccination, would be an important strategy to reduce the risk of infection.6 Assessment of vaccine efficacy against emerging SARS-CoV-2 variants is necessary to establish optimal vaccine strategies for both immunocompetent and immunocompromised populations. Future evaluations of SARS-CoV-2 vaccine platforms in kidney transplant recipients are imperative to confirm safety and immunogenicity, but the expectation is that SARS-CoV-2 vaccines will add to the armamentarium of vaccines that have safely protected transplant recipients from serious infectious diseases for decades. Disclosures A. Limaye reports having consultancy agreements with AlloVir, Amplyx, GSK, Merck, NovaNordisk, Novartis, and Sana Biotech and being a scientific advisor or member with NobelPharma and Novartis. M.R. Heldman reports receiving speaking honoraria from CignaLife Source, outside the scope of the submitted work. Funding This work was supported by the National Institute of Allergy and Infectious Diseases (T32AI118690 to M.R. Heldman). The content of this work is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Periostin (POSTN) plays an important role in numerous cancers, especially in gastrointestinal malignancy. The objective of this study was to investigate the diagnostic and prognostic role of serum POSTN in colorectal cancer (CRC). Serum periostin, together with CEA, CA19.9, CA72.4, and CA242 levels were measured in samples from 108 patients with CRC and 56 healthy controls, and their correlation with clinical characteristics was further analyzed. Receiver operating curves (ROC), Kaplan-Meier curves, and log-rank analyses were used to evaluate diagnostic and prognostic significance. Serum POSTN levels were significantly higher in patients with CRC compared with healthy controls (p < 0.0001) and associated with clinical stages (p < 0.001). ROC analysis revealed that POSTN was a biomarker comparable to CEA, CA19.9, and CA72.4 to distinguish all CRC from healthy controls (AUC = 0.75). Moreover, POSTN retained its diagnostic ability for CEA-negative (AUC = 0.69) and CA19.9-negative CRC patients (AUC = 0.71). Survival analysis revealed that patients with lower serum POSTN had longer overall survival than those with high serum POSTN (p = 0.0146). Serum POSTN might be a novel diagnostic and prognostic biomarker for patients with CRC.