Amplified Type I Interferon Response in Sjögren's Disease via Ectopic Toll-Like Receptor 7 Expression in Salivary Gland Epithelial Cells Induced by Lysosome-Associated Membrane Protein 3.

OBJECTIVE: Lysosome-associated membrane protein 3 (LAMP3) misexpression in salivary gland epithelial cells plays a causal role in the development of salivary gland dysfunction and autoimmunity associated with Sjögren's disease (SjD). This study aimed to clarify how epithelial LAMP3 misexpression is induced in SjD. METHODS: To explore upstream signaling pathways associated with LAMP3 expression, we conducted multiple RNA sequencing analyses of minor salivary glands from patients with SjD, submandibular glands from a mouse model of SjD, and salivary gland epithelial cell lines. A hypothesis generated by the RNA sequencing analyses was further tested by in vitro and in vivo assays with gene manipulation. RESULTS: Transcriptome analysis suggested LAMP3 expression was associated with enhanced type I interferon (IFN) and IFNγ signaling pathways in patients with SjD. In vitro studies showed that type I IFN but not IFNγ stimulation could induce LAMP3 expression in salivary gland epithelial cells. Moreover, we discovered that LAMP3 overexpression could induce ectopic Toll-like receptor 7 (TLR-7) expression and type I IFN production in salivary gland epithelial cells both in vitro and in vivo. TLR-7 knockout mice did not develop any SjD-related symptoms following LAMP3 induction. CONCLUSION: Epithelial LAMP3 misexpression can be induced through enhanced type I IFN response in salivary glands. In addition, LAMP3 can promote type I IFN production via ectopic TLR-7 expression in salivary gland epithelial cells. This positive feedback loop can contribute to maintaining LAMP3 misexpression and amplifying type I IFN production in salivary glands, which plays an essential role in the pathophysiology of SjD.

Diagnostic accuracy of ultrasonography in relation to salivary gland biopsy in Sjögren's syndrome: a systematic review with meta-analysis.

OBJECTIVES: To evaluate the accuracy of major salivary gland ultrasonography (SGUS) in relation to minor salivary gland biopsy (mSGB) in the diagnosis of Sjögren's syndrome (SS). METHODS: A systematic review and meta-analysis were performed. Ten databases were searched to identify studies that compared the accuracy of SGUS and mSGB. The risk of bias was assessed, data were extracted, and univariate and bivariate random-effects meta-analyses were done. RESULTS: A total of 5000 records were identified; 13 studies were included in the qualitative synthesis and 10 in the quantitative synthesis. The first meta-analysis found a sensitivity of 0.86 (95% CI: 0.74-0.92) and specificity of 0.87 (95% CI: 0.81-0.92) for the predictive value of SGUS scoring in relation to the result of mSGB. In the second meta-analysis, mSGB showed higher sensitivity and specificity than SGUS. Sensitivity was 0.80 (95% CI: 0.74-0.85) for mSGB and 0.71 (95% CI: 0.58-0.81) for SGUS, and specificity was 0.94 (95% CI: 0.87-0.97) for mSGB and 0.89 (95% CI: 0.82-0.94) for SGUS. CONCLUSIONS: The diagnostic accuracy of SGUS was similar to that of mSGB. SGUS is an effective diagnostic test that shows good sensitivity and high specificity, in addition to being a good tool for prognosis and for avoiding unnecessary biopsies. More studies using similar methodologies are needed to assess the accuracy of SGUS in predicting the result of mSGB. Our results will contribute to decision-making for the implementation of SGUS as a diagnostic tool for SS, considering the advantages of this method.

Salivary gland LAMP3 mRNA expression is a possible predictive marker in the response to hydroxychloroquine in Sjögren's disease.

Hydroxychloroquine (HCQ) is a lysosomotropic agent that is commonly used for treating Sjögren's disease (SjD). However, its efficacy is controversial because of the divergent response to the drug among patients. In a subgroup of SjD patients, lysosome-associated membrane protein 3 (LAMP3) is elevated in expression in the salivary glands and promotes lysosomal dysregulation and lysosome-dependent apoptotic cell death. In this study, chloroquine (CQ) and its derivative HCQ were tested for their ability to prevent LAMP3-induced apoptosis, in vitro and on a mouse model of SjD. In addition, efficacy of HCQ treatment was retrospectively compared between high LAMP3 mRNA expression in minor salivary glands and those with LAMP3 mRNA levels comparable with healthy controls. Study results show that CQ treatment stabilized the lysosomal membrane in LAMP3-overexpressing cells via deactivation of cathepsin B, resulting in decreased apoptotic cell death. In mice with established SjD-like phenotype, HCQ treatment also significantly decreased apoptotic cell death and ameliorated salivary gland hypofunction. Retrospective analysis of SjD patients found that HCQ tended to be more effective in improving disease activity index, symptom severity and hypergammaglobulinemia in patients with high LAMP3 expression compared those with normal LAMP3 expression. Taken together, these findings suggested that by determining salivary gland LAMP3 mRNA level, a patient's response to HCQ treatment could be predicted. This finding may provide a novel strategy for guiding the development of more personalized medicine for SjD.

Effect of Non-Surgical Periodontal Therapy on Clinical Parameters of Periodontitis, Oral Candida spp. Count and Lactoferrin and Histatin Expression in Saliva and Gingival Crevicular Fluid of HIV-Infected Patients.

BACKGROUND: Periodontitis (PDT) has gained attention in the literature with the increase in life expectancy of people living with HIV on combined antiretroviral therapy (cART). Thus, the search for inflammatory biomarkers could be useful to understand the pathophysiology of chronic oral diseases in the cART era. OBJECTIVE: The aim of this study was to evaluate the impact of non-surgical periodontal therapy (NSPT) on clinical parameters of PDT, Candida spp. count and expression of lactoferrin (LF) and histatin (HST) in saliva and gingival crevicular fluid (GCF) of HIV-infected patients. METHODS: Bleeding index (BI), probing depth (PD), clinical attachment level (CAL), colonyforming units (CFUs) of Candida spp, and LF and HST levels were measured in saliva and GCF of both groups at three different times: baseline (before treatment), and 30 and 90 days after the NSPT. Clinical, mycological and immunoenzymatic analyses were also performed. RESULTS: Twenty-two HIV-infected patients and 25 non-HIV-infected patients with PDT participated in the study. NSPT was effective in improving periodontal clinical parameters, including ≤ 4 sites with PD ≤ 5mm and BI ≤ 10%. Significant change in oral Candida spp. count occurred neither between the two groups nor after NSPT. And the salivary and GCF levels of LF and HST were not influenced by the NSPT; by contrast, except for salivary LF, HST and LF were shown to exhibit significantly higher levels in HIV-infected than in non-HIV-infected patients. CONCLUSION: NSPT was effective in improving periodontal disease parameters in HIV-infected patients, but did not affect LF and HST expression in saliva and GCF of HIV-infected patients.

Clinical and laboratory evaluation of sicca complaints: distinctive aspects of primary, secondary and non-Sjogren syndrome.

BACKGROUND: Sjögren Syndrome (SS) is a systemic autoimmune disease with a wide spectrum of manifestations that can lead to misdiagnosis. This study describes and compares demographic, clinical, serological, and histopathological data from subjects with SS and non-Sjögren Syndrome (NSS). It also details specific features within the primary SS (pSS) and secondary SS (sSS) groups identifying sub-groups. METHODS: The sample included individuals referred to an academic medical center in Brazil for investigation of SS from 2012 to 2020. Patients were retrospectively classified as primary SS (pSS), secondary SS (sSS), or NSS, based on the American-European Consensus Group criteria (AECG-2002), after multi-professional clinical and laboratory evaluation. RESULTS: A total of 676 individuals were screened and 510 (75.4%) completed the assessments; 198 patients were classified as pSS, 149 as sSS, and 163 as NSS. Symptoms and glandular dysfunction tests were similar in the groups. Concerning pSS, extraglandular manifestations were present in 59% of patients; the elderly had more dry symptoms and peripheral neurological disorders; and 2.5% developed non-Hodgkin lymphoma. In sSS, each overlap promoted distinct clinical and laboratory variants. Several alternative diagnoses were identified as a cause of sicca complex in NSS group. CONCLUSIONS: The diagnosis of SS remains a challenge behind dryness. Up to 31% of the suspected cases had other conditions associated to the symptoms. Histopathological analysis of LSG and SSa determined the diagnostic. Aging in pSS and overlap disease in sSS were responsible for distinct phenotypes and characteristic sub-groups in SS.

Lysosomal exocytosis of HSP70 stimulates monocytic BMP6 expression in Sjögren's syndrome.

BMP6 is a central cytokine in the induction of Sjögren's syndrome-associated (SS-associated) secretory hypofunction. However, the upstream initiation leading to the production of this cytokine in SS is unknown. In this study, RNA ISH on salivary gland sections taken from patients with SS indicated monocytic lineage cells as a cellular source of BMP6. RNA-Seq data on human salivary glands suggested that TLR4 signaling was an upstream regulator of BMP6, which was confirmed by in vitro cell assays and single-cell transcriptomics of human PBMCs. Further investigation showed that HSP70 was an endogenous natural TLR4 ligand that stimulated BMP6 expression in SS. Release of HSP70 from epithelial cells could be triggered by overexpression of lysosome-associated membrane protein 3 (LAMP3), a protein also associated with SS in several transcriptome studies. In vitro studies supported the idea that HSP70 was released as a result of lysosomal exocytosis initiated by LAMP3 expression, and reverse transcription PCR on RNA from minor salivary glands of patients with SS confirmed a positive correlation between BMP6 and LAMP3 expression. BMP6 expression could be experimentally induced in mice by overexpression of LAMP3, which developed an SS-like phenotype. The newly identified LAMP3/HSP70/BMP6 axis provided an etiological model for SS gland dysfunction and autoimmunity.

Non-surgical periodontal debridement affects subgingival bacterial diversity in patients with HIV-1 and periodontitis.

BACKGROUND: Following human immunodeficiency virus-1 (HIV-1) infection and antiretroviral therapy, the development of periodontal disease was shown to be favored. However, the influence of HIV-1 infection on the periodontal microbiota after non-surgical periodontal debridement (NSPD) needs a broad comprehension. This work aimed to compare the subgingival microbiological content of patients infected with HIV-1 and controls (non-infected) with periodontitis undergoing NSPD. METHODS: The bacterial profile of subgingival biofilm samples of patients with HIV-1 (n = 18) and controls (n = 14) with periodontitis was assessed using 16S rRNA gene sequencing. The samples were collected at baseline, 30, and 90 days after NSPD. The taxonomic analysis of gingival microbiota was performed using a ribosomal RNA database. The microbiota content was evaluated in the light of CD4 cell count and viral load. RESULTS: Both HIV and control groups showed similar stages and grades of periodontitis. At baseline, the HIV group showed higher alpha diversity for both healthy and periodontal sites. Streptococcus, Fusobacterium, Veillonella and Prevotella were the predominant bacterial genera. A low abundance of periodontopathogenic bacteria was observed, and the NSPD induced shifts in the subgingival biofilm of patients with HIV-1, leading to a microbiota similar to that of controls. CONCLUSIONS: Different subgingival microbiota profiles were identified-a less diverse microbiota was found in patients infected with HIV-1, in contrast to a more diverse microbiota in controls. NSPD caused changes in the microbiota of both groups, with a greater impact on the HIV group, leading to a decrease in alpha diversity, and produced a positive impact on the serological immune markers in patients infected with HIV-1. Control of periodontitis should be included as part of an oral primary care, providing the oral health benefits and better control of HIV-1 infection.

Gingival tissue as a reservoir for human immunodeficiency virus type 1: Preliminary results of a cross-sectional observational study.

BACKGROUND: Despite combined antiretroviral therapy (cART), total cure of immunodeficiency virus type 1 (HIV-1) infection remains elusive. Chronic periodontitis (CP) is strongly associated with HIV-1 infection. This condition is characterized by an intense inflammatory infiltrate mainly constituted of immune cells which in turn may be a valuable source of HIV-1 reactivation. This study aimed to determine if gingival tissue could act as a reservoir for HIV-1. METHODS: Twelve patients with HIV-1 and CP and 12 controls (no HIV-1-infection and no CP) were evaluated in a cross-sectional study. RNA viral load and interleukin (IL) levels were determined in blood plasma and saliva. Histological sections of gingival tissue were stained with fluorescent antibodies against p24 antigen and different cellular biomarkers. RESULTS: In six of the 12 patients, HIV RNA load was detected, despite cART; in three of them, expression of viral RNA was also detected in saliva. The levels of IL-2, IL-6, and IL-12 were higher in blood and saliva of patients with HIVand CP than controls. HIV-1 p24 antigen was detected by immunostaining in gingival biopsies of 10 of the 12 patients but in no controls. Immune markers for T cells and antigen-presenting cells were also identified in most patients and some controls. CONCLUSION: These preliminary data showing the detection of HIV-1 p24 antigen in the gingival biopsies of a significant part of patients with HIV-1 and CP under cART together with the presence of immune cells, plead for the existence of a HIV-1 reservoir in the gingival tissue of this population.

LAMP3 induces apoptosis and autoantigen release in Sjögren's syndrome patients.

Primary Sjögren's syndrome (pSS) is a complex autoimmune disease characterized by dysfunction of secretory epithelia with only palliative therapy. Patients present with a constellation of symptoms, and the diversity of symptomatic presentation has made it difficult to understand the underlying disease mechanisms. In this study, aggregation of unbiased transcriptome profiling data sets of minor salivary gland biopsies from controls and Sjögren's syndrome patients identified increased expression of lysosome-associated membrane protein 3 (LAMP3/CD208/DC-LAMP) in a subset of Sjögren's syndrome cases. Stratification of patients based on their clinical characteristics suggested an association between increased LAMP3 expression and the presence of serum autoantibodies including anti-Ro/SSA, anti-La/SSB, anti-nuclear antibodies. In vitro studies demonstrated that LAMP3 expression induces epithelial cell dysfunction leading to apoptosis. Interestingly, LAMP3 expression resulted in the accumulation and release of intracellular TRIM21 (one component of SSA), La (SSB), and α-fodrin protein, common autoantigens in Sjögren's syndrome, via extracellular vesicles in an apoptosis-independent mechanism. This study defines a clear role for LAMP3 in the initiation of apoptosis and an independent pathway for the extracellular release of known autoantigens leading to the formation of autoantibodies associated with this disease.ClinicalTrials.gov Identifier: NCT00001196, NCT00001390, NCT02327884.

Effects of non-surgical periodontal therapy on clinical and immunological profile and oral colonization of Candida spp in HIV-infected patients with chronic periodontitis.

BACKGROUND: After the introduction of antiretroviral therapy (ART), human immunodeficiency virus (HIV) infection has become a chronic controllable disease. For this reason, chronic conditions related to both HIV infection and senescence, such as chronic periodontitis (CP) need to be studied. This study investigated the impact of non-surgical periodontal therapy (NSPT) on clinical and immunological features of CP, and on oral colonization by Candida spp. in HIV-infected and non-HIV-infected individuals. METHODS: HIV-infected (test group) and non-HIV-infected (control group) adults patients with CP were selected. Gingival bleeding index (GI), probing depth (PD), clinical attachment level (CAL), number of teeth, CD4+ T lymphocytes and viral load (only for HIV-infected individuals), salivary cytokines (interleukin, [IL]-6, IL-8, and tumoral necrosis factor-alpha [TNF-α]), and oral Candida infection (colony forming units and species) were assessed at baseline, and 30 and 90 days after NSPT. RESULTS: Twenty-two HIV-infected patients and 20 non-HIV-infected patients were evaluated. Candida counts and salivary IL-6, IL-8, and TNF-a levels were higher in the test group than in the control group. Both groups showed a decrease in oral Candida counts, GI, PD, IL-6, and IL-8 as well as gain in CAL at 30 and 90 days after NSPT. In addition, patients in the test group showed an increase of CD4+ T lymphocytes and a decrease of viral load. CONCLUSION: NSPT had a beneficial impact on clinical and immunological parameters of CP, reduction of oral Candida counts, and improvement of HIV-infection status.

Relationship between human immunodeficiency virus (HIV-1) infection and chronic periodontitis.

INTRODUCTION: Current studies show that, even in the era of antiretroviral therapies, HIV-1 infection is associated with more severe and frequent refractory chronic periodontitis. Areas covered: This review, based on a systematic analysis of the literature, intends to provide an update on factors that may be involved in the pathogenesis of periodontal disease in HIV-1-infected patients, including local immunosuppression, oral microbial factors, systemic inflammation, salivary markers, and the role of gingival tissue as a possible reservoir of HIV-1. Expert commentary: The therapeutic revolution of ART made HIV-1 infection a chronic controllable disease, reduced HIV-1 mortality rate, restored at least partially the immune response and dramatically increased life expectancy of HIV-1-infected patients. Despite all these positive aspects, chronic periodontitis assumes an important role in the HIV-1 infection status for activating systemic inflammation favoring viral replication and influencing HIV-1 status, and also acting as a possible reservoir of HIV-1. All these issues still need to be clarified and validated, but have important clinical implications that certainly will benefit the diagnosis and management of chronic periodontitis in HIV-1-infected patients, and also contributes to HIV-1 eradication.

Donor CD19 CAR T cells exert potent graft-versus-lymphoma activity with diminished graft-versus-host activity.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative therapy for hematological malignancies. However, graft-versus-host disease (GVHD) and relapse after allo-HSCT remain major impediments to the success of allo-HSCT. Chimeric antigen receptors (CARs) direct tumor cell recognition of adoptively transferred T cells. CD19 is an attractive CAR target, which is expressed in most B cell malignancies, as well as in healthy B cells. Clinical trials using autologous CD19-targeted T cells have shown remarkable promise in various B cell malignancies. However, the use of allogeneic CAR T cells poses a concern in that it may increase risk of the occurrence of GVHD, although this has not been reported in selected patients infused with donor-derived CD19 CAR T cells after allo-HSCT. To understand the mechanism whereby allogeneic CD19 CAR T cells may mediate anti-lymphoma activity without causing a significant increase in the incidence of GVHD, we studied donor-derived CD19 CAR T cells in allo-HSCT and lymphoma models in mice. We demonstrate that alloreactive T cells expressing CD28-costimulated CD19 CARs experience enhanced stimulation, resulting in the progressive loss of both their effector function and proliferative potential, clonal deletion, and significantly decreased occurrence of GVHD. Concurrently, the other CAR T cells that were present in bulk donor T cell populations retained their anti-lymphoma activity in accordance with the requirement that both the T cell receptor (TCR) and CAR be engaged to accelerate T cell exhaustion. In contrast, first-generation and 4-1BB-costimulated CAR T cells increased the occurrence of GVHD. These findings could explain the reduced risk of GVHD occurring with cumulative TCR and CAR signaling.

Leprosy reactions: coinfections as a possible risk factor.

OBJECTIVE: This study aimed to determine the frequency of coinfections in leprosy patients and whether there is a relationship between the presence of coinfections and the development of leprosy reactional episodes. METHOD: A cross-sectional study based on an analysis of the medical records of the patients who were treated at the Leprosy Clinics of the Ribeirão Preto Medical School, University of São Paulo, was conducted from 2000 to 2010. Information was recorded regarding the age, sex, clinical status, WHO classification, treatment, presence of reactions and coinfections. Focal and systemic infections were diagnosed based on the history, physical examination, and laboratory tests. Multinomial logistic regression was used to evaluate the associations between the leprosy reactions and the patients' gender, age, WHO classification and coinfections. RESULTS: Two hundred twenty-five patients were studied. Most of these patients were males (155/225 = 68.8%) of an average age of 49.31±15.92 years, and the most prevalent clinical manifestation was the multibacillary (MB) form (n = 146), followed by the paucibacillary (PB) form (n = 79). Erythema nodosum leprosum (ENL) was more prevalent (78/122 = 63.9%) than the reversal reaction (RR) (44/122 = 36.1%), especially in the MB patients (OR 5.07; CI 2.86-8.99; p<0.0001) who exhibited coinfections (OR 2.26; CI 1.56-3.27; p<0.0001). Eighty-eight (88/225 = 39.1%) patients exhibited coinfections. Oral coinfections were the most prevalent (40/88 = 45.5%), followed by urinary tract infections (17/88 = 19.3%), sinusopathy (6/88 = 6.8%), hepatitis C (6/88 = 6.8%), and hepatitis B (6/88 = 6.8%). CONCLUSIONS: Coinfections may be involved in the development and maintenance of leprosy reactions.

Leprosy reactions: coinfections as a possible risk factor

OBJECTIVE: This study aimed to determine the frequency of coinfections in leprosy patients and whether there is a relationship between the presence of coinfections and the development of leprosy reactional episodes. METHOD: A cross-sectional study based on an analysis of the medical records of the patients who were treated at the Leprosy Clinics of the Ribeirão Preto Medical School, University of São Paulo, was conducted from 2000 to 2010. Information was recorded regarding the age, sex, clinical status, WHO classification, treatment, presence of reactions and coinfections. Focal and systemic infections were diagnosed based on the history, physical examination, and laboratory tests. Multinomial logistic regression was used to evaluate the associations between the leprosy reactions and the patients' gender, age, WHO classification and coinfections. RESULTS: Two hundred twenty-five patients were studied. Most of these patients were males (155/225 = 68.8%) of an average age of 49.31±15.92 years, and the most prevalent clinical manifestation was the multibacillary (MB) form (n = 146), followed by the paucibacillary (PB) form (n = 79). Erythema nodosum leprosum (ENL) was more prevalent (78/122 = 63.9%) than the reversal reaction (RR) (44/122 = 36.1%), especially in the MB patients (OR 5.07; CI 2.86-8.99; p<0.0001) who exhibited coinfections (OR 2.26; CI 1.56-3.27; p,<0.0001). Eighty-eight (88/225 = 39.1%) patients exhibited coinfections. Oral coinfections were the most prevalent (40/88 = 45.5%), followed by urinary tract infections (17/88 = 19.3%), sinusopathy (6/88 = 6.8%), hepatitis C (6/88 = 6.8%), and hepatitis B (6/88 = 6.8%). CONCLUSIONS: Coinfections may be involved in the development and maintenance of leprosy reactions.

Oral lesions associated with HIV infection before and during the antiretroviral therapy era in Ribeirão Preto, Brazil.

We estimated the prevalence of oral lesions associated with human immunodeficiency virus (HIV-OLs) before and during the antiretroviral therapy (ART) era. The first period was 1997, when many patients received two types of antiretroviral (ARV) drugs. The second study period was 2004 through 2008, when all patients were treated with ART (a combination of two or three classes of drugs, including protease inhibitors). A total of 148 and 388 seropositive participants were examined in 1997 and 2004-2008, respectively. The evaluation consisted of anamnesis and physical examination. The prevalence of HIV-OLs decreased between 1997 (60.1%) and 2004-2008 (29.9%). The HIV-OL responsible for the greatest reduction in prevalence between the two periods was oral candidiasis, of which erythematous candidiasis was the clinical form that decreased most, followed by pseudomembranous candidiasis. In conclusion, we observed a significant reduction in HIV-OLs, which was closely associated with the use of ART. In addition, among patients with a clinical diagnosis of AIDS, we confirmed a significant reduction in HIV-OL prevalence between 1997 and 2004-2008.

Early detection of leprosy by examination of household contacts, determination of serum anti-PGL-1 antibodies and consanguinity.

A cross-sectional clinical trial in which the serum anti-phenolic glycolipid (anti-PGL-1) antibodies were analysed in household contacts (HHC) of patients with leprosy as an adjunct early leprosy diagnostic marker was conducted. The families of 83 patients underwent clinical examination and serum anti-PGL1 measurement using enzyme-linked immunosorbent assay. Of 320 HHC, 98 were contacts of lepromatous leprosy (LL), 80 were contacts of borderline lepromatous (BL), 28 were contacts of borderline (BB) leprosy, 54 were contacts of borderline tuberculoid (BT), 40 were contacts of tuberculoid (TT) and 20 were contacts of indeterminate (I) leprosy. Consanguinity with the patients was determined for 232 (72.5%) HHC. Of those 232 contacts, 183 had linear consanguinity. Forty-nine HHC had collateral consanguinity. Fifty-eight contacts (18.1%) tested positive for anti-PGL1 antibodies. The number of seropositive contacts based on the clinical forms of the index case was 17 (29.3%) for LL, 15 (25.9%) for BL, one (1.7%) for BB, 14 (24.1%) for BT, three (5.2%) for TT and eight (13.7%) for I. At the one year follow-up, two (3.4%) of these seropositive contacts had developed BT leprosy. The results of the present study indicate that the serum anti-PGL-1 IgM antibody may be useful for evaluating antigen exposure and as a tool for an early leprosy diagnosis in HHC.

Early detection of leprosy by examination of household contacts, determination of serum anti-PGL-1 antibodies and consanguinity

A cross-sectional clinical trial in which the serum anti-phenolic glycolipid (anti-PGL-1) antibodies were analysed in household contacts (HHC) of patients with leprosy as an adjunct early leprosy diagnostic marker was conducted. The families of 83 patients underwent clinical examination and serum anti-PGL1 measurement using enzyme-linked immunosorbent assay. Of 320 HHC, 98 were contacts of lepromatous leprosy (LL), 80 were contacts of borderline lepromatous (BL), 28 were contacts of borderline (BB) leprosy, 54 were contacts of borderline tuberculoid (BT), 40 were contacts of tuberculoid (TT) and 20 were contacts of indeterminate (I) leprosy. Consanguinity with the patients was determined for 232 (72.5 percent) HHC. Of those 232 contacts, 183 had linear consanguinity. Forty-nine HHC had collateral consanguinity. Fifty-eight contacts (18.1 percent) tested positive for anti-PGL1 antibodies. The number of seropositive contacts based on the clinical forms of the index case was 17 (29.3 percent) for LL, 15 (25.9 percent) for BL, one (1.7 percent) for BB, 14 (24.1 percent) for BT, three (5.2 percent) for TT and eight (13.7 percent) for I. At the one year follow-up, two (3.4 percent) of these seropositive contacts had developed BT leprosy. The results of the present study indicate that the serum anti-PGL-1 IgM antibody may be useful for evaluating antigen exposure and as a tool for an early leprosy diagnosis in HHC.

The recurrence of leprosy reactional episodes could be associated with oral chronic infections and expression of serum IL-1, TNF-alpha, IL-6, IFN-gamma and IL-10.

The aim of this study was to determine whether the presence of leprosy reactional episodes could be associated with chronic oral infection. Thirty-eight leprosy patients were selected and divided into 2 groups: group I - 19 leprosy patients with oral infections, and group II - 19 leprosy patients without oral infections. Ten patients without leprosy, but presenting oral infections, were assigned to the control group. Leprosy patients were classified according to Ridley and Jopling classification and reactional episodes of the erythema nodosum type or reversal reaction were identified by clinical and histopathological features associated with serum IL-1, TNF-alpha, IL-6, IFN-gamma and IL-10 levels. These analyses were performed immediately before and 7 days after the oral infection elimination. Patients from group I presenting oral infections reported clinical improvement of the symptoms of reactional episodes after dental treatment. Serum IL-1, TNF-alpha, IL-6, IFN-gamma and IL-10 levels did not differ significantly before and after dental treatment as determined by the Wilcoxon test (p>0.05). Comparison of the 2 groups showed statistically significant differences in IL-1 and IL-6 at baseline and in IL-1, IL-6 and IL-10 on the occasion of both collections 7 days after therapy. Serum IL-6 and IL-10 levels in group I differed significantly at baseline compared to control (Mann-Whitney test; p<0.05). These results suggest that oral infection could be involved as a maintenance factor in the pathogenesis of leprosy reactional episodes.

The recurrence of leprosy reactional episodes could be associated with oral chronic infections and expression of serum IL-1, TNF-á, IL-6, IFN-ã and IL-10

The aim of this study was to determine whether the presence of leprosy reactional episodes could be associated with chronic oral infection. Thirty-eight leprosy patients were selected and divided into 2 groups: group I - 19 leprosy patients with oral infections, and group II - 19 leprosy patients without oral infections. Ten patients without leprosy, but presenting oral infections, were assigned to the control group. Leprosy patients were classified according to Ridley and Jopling classification and reactional episodes of the erythema nodosum type or reversal reaction were identified by clinical and histopathological features associated with serum IL-1, TNF-?, IL-6, IFN-? and IL-10 levels. These analyses were performed immediately before and 7 days after the oral infection elimination. Patients from group I presenting oral infections reported clinical improvement of the symptoms of reactional episodes after dental treatment. Serum IL-1, TNF-?, IL-6, IFN-? and IL-10 levels did not differ significantly before and after dental treatment as determined by the Wilcoxon test (p>0.05). Comparison of the 2 groups showed statistically significant differences in IL-1 and IL-6 at baseline and in IL-1, IL-6 and IL-10 on the occasion of both collections 7 days after therapy. Serum IL-6 and IL-10 levels in group I differed significantly at baseline compared to control (Mann-Whitney test; p<0.05). These results suggest that oral infection could be involved as a maintenance factor in the pathogenesis of leprosy reactional episodes.

O objetivo deste estudo foi determinar se os episódios reacionais da hanseníase podem estar associados a infecções orais crônicas. Trinta e oito pacientes com hanseníase foram selecionados e divididos em dois grupos: grupo I & 19 pacientes com hanseníase apresentando infecções orais, e grupo II & 19 pacientes com hanseníase sem infecções orais. Os pacientes foram classificados, quanto à forma clínica da doença, de acordo com Ridley and Jopling, e os episódios reacionais, tipo eritema nodoso e reação reversa, foram identificados pelas características clínicas, histopatológicas associadas à quantificação no soro de IL-1, TNF-?, IL-6, IFN-? e IL-10. Estas analises foram realizadas imediatamente antes e 7 dias após a resolução dos focos de infecção. Pacientes do grupo I aprentando infecções orais relataram melhora clínica dos sintomas dos episódios reacionais após o tratamento odontológico. Os níveis séricos de IL-1, TNF-?, IL-6, IFN-? e IL-10 não diferiram significantemente antes e após o tratamento odontológico, como determinado pelo teste Wilcoxon (p>0,05). As comparações entre os grupos mostrou diferenças estatisticamente significantes nos níveis de IL-1 e IL-6 na coleta inicial e nos níveis de IL-1, IL-6 e IL-10 nas duas coletas 7 dias após o tratamento (teste Mann-Whitney; p<0,05). Estes resultados sugerem que infecções orais estão envolvidas na patogênese dos episódios reacionais da hanseníase, como fatores mantenedores.