T-independent antigen induces humoral memory through germinal centers

T-dependent humoral responses generate long-lived memory B cells and plasma cells (PCs) predominantly through germinal center (GC) reaction. In human and mouse, memory B cells and long-lived PCs are also generated during immune responses to T-independent antigen, including bacterial polysaccharides, although the underlying mechanism for such T-independent humoral memory is not clear. While T-independent antigen can induce GCs, they are transient and thought to be nonproductive. Unexpectedly, by genetic fate-mapping, we find that these GCs actually output memory B cells and PCs. Using a conditional BCL6 deletion approach, we show memory B cells and PCs fail to last when T-independent GCs are precluded, suggesting that the GC experience per se is important for programming longevity of T-independent memory B cells and PCs. Consistent with the fact that infants cannot mount long-lived humoral memory to T-independent antigen, B cells from young animals intrinsically fail to form T-independent GCs. Our results suggest that T-independent GCs support humoral memory, and GC induction may be key to effective vaccines with T-independent antigen.

Low prevalence of anti-SSA (anti-Ro) and anti-SSB (anti-La) autoantibodies in female patients with rheumatoid arthritis with a wish to conceive

ObjectivesGuidelines advise to test for anti–Sjögren's-syndrome-related antigen A (anti-SSA) and anti–Sjögren's-syndrome-related antigen B (anti-SSB) antibodies in all patients with rheumatoid arthritis (RA) who wish to conceive. Our objective was to determine the prevalence and titres of anti-SSA and anti-SSB autoantibodies in patients with RA with a wish to conceive or pregnant.MethodsPatients were derived from two large cohorts on RA and pregnancy (PARA cohort and PreCARA cohort). In addition, to determine the clinical relevance of searching for anti-SSA and anti-SSB in patients with RA, we studied the prevalence of the maternal diagnosis of RA in the French national registry of neonatal lupus syndrome (NLS) and congenital heart block (CHB).Results26 out of 647 patients with RA had detectable anti-SSA and/or anti-SSB. Anti-SSA was detected in 25 out of 647 patients (3.9%) (Ro-52, n=17; Ro-60, n=19), anti-SSB in 7 out of 647 (1.1%). Thirteen women had a titre of >240 units/mL of anti-SSA antibodies. The prevalence of anti-SSA and/or anti-SSB was higher in rheumatoid factor (RF)-positive patients compared with RF-negative patients (5.1% vs 1.6%, p=0.04). No cases of CHB and/or NLS in the offspring were observed. In the French national register, the prevalence of RA in mothers with SSA related CHB was 1.5%.ConclusionAnti-SSA and anti-SSB have a low prevalence in patients with RA who wish to conceive. Especially for RF-negative patients, the current advise to test for anti-SSA and anti-SSB should be reconsidered.

The Diagnosis of Sheep Cystic Echinococcosis by Native Antigen B - ELISA Method

Cystic echinococcosis (CE) is one of the most prevalent zoonotic diseases in some countries in the world. Cystic echinococcosis is considered a neglected disease. This disease increases economic damage via medical costs and loss of human and livestock productivity. The aim of the current study gains a better understanding of the prevalence of CE in sheep. Totally 250 sheep sera were collected. 25 serum samples from newborn lambs were used as negative, and 25 others were obtained from slaughterhouses as positive to infection with CE and 200 unknown sera. Antigen B Isolated from hydatid cysts fluid was used for designing ELISA methods. The first Method used anti-Sheep conjugate (SIGMA, at 1:3000 dilution). According to the results, the seroprevalence of CE in East Azerbaijan of Iran was 5.5% and sensitivity and specificity for the diagnosis of hydatidosis in sheep by AgB-ELISA methods was 92%. Using Antigen B in ELISA design for hydatidosis diagnosis has attracted researchers in recent years. During this study, an Iranian native B antigen was used to design the specific detection of hydatidosis in sheep using a specific ELISA technique. The results have shown that using Antigen B in ELISA design is so valuable.

Seroprevalence of Cystic Echinococcosis Using Recombinant Antigen B-ELISA in North Khorasan Province, Northeast of Iran

Background: Cystic echinococcosis (CE) is one of the most important helminthic parasitic diseases in Iran. The current study aimed to assess the seroprevalence of CE in North Khorasan Province, Northeast of Iran in 2018. Methods: The study was carried out in seven cities of North Khorasan Province. Venous blood samples were collected from 932 individuals referring to health centers of those seven cities. A questionnaire was used to obtain the data regarding the subject's gender, age, residence and risk factors linked to the hydatid cyst. Sera samples were evaluated for anti-hydatid cyst antibodies in an ELISA system, using a recombinant B8/1 antigen of E. granulosus. Results: Of the 932 recruited subjects, 496 (53.2%) were male and 436 (46.8%) were female. The range of participants’ age was between 11 to 83 yr old and the mean age of the subjects was 35.4 (±12.7) years. Anti-hydatid cyst antibodies were detected in the sera of 37 out of 932 subjects, corresponding to a seroprevalence rate of 3.96%. From these, 20 (54.05%) were male and 17 (45.95%) were female. There were no associations between seropositivity to hydatid cyst and age, the gender of the participants, residential areas and having contact with dogs (P>0.05). Conclusion: CE is relatively prevalent throughout the North Khorasan Province in the Northeast of Iran. Rate of CE infection in this Province is somewhat similar to the rate of infection in other parts of the country.

T Cell Mediated Conversion of a Non-Anti-La Reactive B Cell to an Autoreactive Anti-La B Cell by Somatic Hypermutation

Since the first description of nuclear autoantigens in the late 1960s and early 1970s, researchers, including ourselves, have found it difficult to establish monoclonal antibodies (mabs) against nuclear antigens, including the La/SS-B (Sjögrens’ syndrome associated antigen B) autoantigen. To date, only a few anti-La mabs have been derived by conventional hybridoma technology; however, those anti-La mabs were not bona fide autoantibodies as they recognize either human La specific, cryptic, or post-translationally modified epitopes which are not accessible on native mouse La protein. Herein, we present a series of novel murine anti-La mabs including truly autoreactive ones. These mabs were elicited from a human La transgenic animal through adoptive transfer of T cells from non-transgenic mice immunized with human La antigen. Detailed epitope and paratope analyses experimentally confirm the hypothesis that somatic hypermutations that occur during T cell dependent maturation can lead to autoreactivity to the nuclear La/SS-B autoantigen.

Raltegravir-associated Drug-Reaction With Eosinophilia and Systemic Symptoms Syndrome in a Pediatric Patient Without Characteristic Human Leukocyte Antigen B*57:01 or B*53:01 alleles

We present the first published case of raltegravir-associated drug-reaction with eosinophilia and systemic symptoms (DRESS) syndrome in a child without characteristic human leukocyte antigen haplotypes HLA-B*57:01 or HLA-B*53:01. A 4-year-old African American female with perinatally acquired human immunodeficiency virus infection was hospitalized for DRESS after starting a raltegravir-based antiretroviral regimen.

Comparative evaluation of IS6110 and protein antigen b PCR in cerebrospinal fluid for rapid diagnosis of tuberculous meningitis in children

Introduction. Childhood tuberculosis meningitis is a severe form of tuberculosis with high morbidity and mortality. The diagnosis is frequently missed and delayed due to lack of sensitive tests like acid-fast bacilli (AFB) smear and delayed results by culture. Aims. To compare the role of IS6110 and protein antigen b PCR in cerebrospinal fluid (CSF) for rapid diagnosis of tuberculous meningitis (TBM) in children. Methodology. Forty-five cases of TBM and 20 controls were enrolled in this prospective study. Results. The mean ages of cases and controls were 4.2±0.5 years and 4.5±0.7 years, respectively. In the TBM group, two-thirds of the children were <4 years of age, and 62 % were males. Sensitivities of AFB smear examination, Löwenstein–Jensen (LJ) medium and bactenecin (BACTEC) culture in cases were 4.4, 0 and 2.2%, respectively. The protein antigen b PCR was most sensitive as it was positive in 35 (77.8 %) of TBM patients; IS6110 PCR was positive in 27 (60 %) patients. Both PCR-based tests had higher positivity than conventional tests and BACTEC culture. No significant difference was seen between the PCR tests. Excellent agreement was observed between both PCR-based tests as they were concordant for 26 positive samples and 35 negative samples. Conclusion. Protein b PCR is a sensitive and rapid method for the diagnosis of TBM (sensitivity 77.8 %). Both PCRs were more sensitive than smear, LJ and BACTEC. The specificity of both PCR was 100 %.