Highly Specific Memory B Cells Generation after the 2nd Dose of BNT162b2 Vaccine Compensate for the Decline of Serum Antibodies and Absence of Mucosal IgA.

Specific memory B cells and antibodies are a reliable read-out of vaccine efficacy. We analysed these biomarkers after one and two doses of BNT162b2 vaccine. The second dose significantly increases the level of highly specific memory B cells and antibodies. Two months after the second dose, specific antibody levels decline, but highly specific memory B cells continue to increase, thus predicting a sustained protection from COVID-19. We show that although mucosal IgA is not induced by the vaccination, memory B cells migrate in response to inflammation and secrete IgA at mucosal sites. We show that the first vaccine dose may lead to an insufficient number of highly specific memory B cells and low concentration of serum antibodies, thus leaving vaccinees without the immune robustness needed to ensure viral elimination and herd immunity. We also clarify that the reduction of serum antibodies does not diminish the force and duration of the immune protection induced by vaccination. The vaccine does not induce sterilizing immunity. Infection after vaccination may be caused by the lack of local preventive immunity because of the absence of mucosal IgA.

Reduced frequency of melanoma in 72,739 patients with psoriasis: A retrospective study.

BACKGROUND: Chronic inflammatory conditions such as psoriasis may pose an increased risk of cancer due to impaired immunosurveillance resulting from the chronic inflammation and immunosuppressive medications. However, the relationship between psoriasis and the risk of melanoma is still controversial. OBJECTIVE: To compare the occurrence of melanoma in a cohort of 72,739 psoriasis patients and in 25,956 non-dermatological patients. METHODS: A record-linkage was performed between records of hospitalizations and access to day-hospital and day-surgery clinics and outpatient clinics. The frequency of melanoma was compared between psoriasis patients and vascular surgery patients. Occurrence of melanoma was compared by computing the relative risk (RR) and modelled using multiple logistic regression. RESULTS: Overall, occurrence of melanoma was 1.8% (95% CI 1.5-2.2%) in psoriasis patients and 4.5% (95% CI 3.8-5.4%) in non-dermatological patients (RR = 0.40, 95% CI 0.31-0.51). The simultaneous adjustment for gender, age, and phototherapy yielded a RRadj = 0.54(95% CI 0.41-0.70. For patients who underwent phototherapy, vs. those who did not, the RRadj was 1.50 (95% CI 0.56-4.15). CONCLUSIONS: In this large retrospective study, patients with psoriasis had a significantly lower probability of having melanoma when compared to a group of non-dermatological patients. Further studies, preferably with a concurrent longitudinal design to estimate incidence with more complete information, are needed to corroborate our findings.

Tumor-infiltrating lymphocytes predict cutaneous melanoma survival.

Understanding differences in survival across distinct subgroups of melanoma patients may help with the choice of types of therapy. Tumor-infiltrating lymphocytes (TILs) are considered a manifestation of the host immune response to tumor, but the role of TILs in melanoma mortality is controversial. The aim of this study was to investigate independent prognostic factors for melanoma mortality. We carried out a 10-year cohort study on 4133 melanoma patients from the same geographic area (Lazio) with primary cutaneous melanoma diagnosed between January 1998 and December 2008. The probability of survival was estimated using Kaplan-Meier methods and prognostic factors were evaluated by multivariate analysis (Cox proportional hazards model). The 10-year survival rate for melanoma decreased with increasing Breslow thickness (Pfor trend<0.0001) and with age (Pfor trend<0.0001) whereas survival increased with increasing levels of TILs (Pfor trend=0.0001). The 10-year survival rate for melanoma divided into TILs intensity as scanty, moderate, and marked was 88.0, 92.2, and 97.0%, respectively. In the multivariate Cox model, the presence of high levels of TILs in primary invasive melanomas was associated with a lower risk of melanoma death (hazard ratio 0.32; 95% confidence interval 0.13-0.82) after controlling for sex, age, Breslow thickness, histological type, mitotic rate, and ulceration. After including lymph node status in the multivariate analysis, the protective effect of marked TILs on melanoma mortality remained (hazard ratio 0.37; 95% confidence interval 0.15-0.94). The results of this study suggest that the immune microenvironment affects melanoma survival.

Single TCR-Vß2 evaluation discloses the circulating T cell clone in Sezary syndrome: one family fits all!

Sézary Syndrome (SS/L-CTCL) is a rare but aggressive variant of cutaneous T cell lymphoma (CTCL), characterized by erythroderma, lymphadenopathy, and the presence of a circulating memory CD4(+) T cell malignant clone with a skin homing behavior, lacking CD26 and CD49d and over-expressing CD60. The availability of a panel of monoclonal antibodies recognizing distinct TCR-Vß families, allows to typify the clone by flow cytometry in about 70 % of cases. The TCR-Vß repertoire of 533 individuals, comprising 308 patients affected by CTCL, 50 healthy donors, and subjects affected by various non-neoplastic dermatological affections was evaluated by flow cytometry. Statistical analyses were performed using the SPSS statistical software package for Microsoft Windows (SPSS, version 21, Chicago, IL). TCR-Vß2 levels below 5.4 % or above 39.5 %, within total CD4(+) T cells, showed the best balance between sensitivity (98.1 %) and specificity (96 %) to identify the presence of a clone in the peripheral blood of patients affected by SS. Based on this observation, a "two-step" procedure in the detection of the malignant T cell clone in CTCLs is herein suggested. TCR-Vß2 assessment in all cases (first step). In the case of TCR-Vß2 levels above 39.5 %, the presence of a clonal expansion of this family is suggested, deserving further confirmation by means of T cell gene rearrangement evaluation. In patients having a TCR-Vß2 reactivity below 5.4 % (second step), the entire TCR-Vß repertoire should be evaluated to typify the expanded clone. In conclusion, the single TCR-Vß2 expression check, instead of the entire repertoire assessment, represents an easy and cost-effective method for the recognition of CTCL aggressive leukemic variant.

Markedly reduced incidence of melanoma and nonmelanoma skin cancer in a nonconcurrent cohort of 10,040 patients with vitiligo.

BACKGROUND: Genetic findings suggesting a lower susceptibility to melanoma in patients with vitiligo are supported by recent clinical studies. Nonmelanoma skin cancer (NMSC) has also been studied, but mainly in small samples, and with conflicting results. OBJECTIVE: We sought to study the relative risk (RR) of melanoma and NMSC in patients with vitiligo compared with that in patients seen for vascular surgery. METHODS: The frequency of melanoma and NMSC was compared between patients with vitiligo and patients seen for vascular surgery. Occurrence of skin cancer was compared by computing RR and modeled using multiple logistic regression. RESULTS: Overall, the crude RR for melanoma was 0.24 (95% confidence interval [CI] 0.13-0.45) in patients with vitiligo compared with those with a nondermatologic condition (occurrence 1.1‰, 95% CI 0.5‰-2.0‰ in patients with vitiligo and occurrence 4.5‰, 95% CI 3.8‰-5.4‰ in the control cohort). The crude RR for NMSC was 0.19 (95% CI 0.14-0.17) and the occurrence was 3.8‰ (95% CI 2.7‰-5.2‰) among patients with vitiligo and 19.6‰ (95% CI 18.0‰-21.4‰) in control subjects. Patients with vitiligo who underwent phototherapy had a markedly higher risk of both cancers. CONCLUSIONS: In our large study, patients with vitiligo have a decreased risk of developing skin neoplasms, even considering that a larger proportion in this patient group is exposed to higher levels of ultraviolet radiation.