Pulmonary Embolism in COVID-19 Patients Is Not Related to a Deterioration of Tissue Oxygenation.

BACKGROUND: COVID-19 induces robust systemic inflammation. One of the main complications is the increased coagulation due to endotheliitis. There is an increased incidence of pulmonary embolism (PE) in COVID-19 patients. However, clinical characteristics for a strict analysis are yet to be determined. AIM: We evaluated oxygenation and characteristics in patients with COVID-19 PE (CPE). MATERIAL AND METHODS: We evaluated 215 COVID-19 patients from 1 January to 30 April 2021. We found 18 patients affected by PE (CPE, 50.0% males, aged 67.00 ± 10.86 years). As controls, we used data from patients affected by PE evaluated in our ward between 1 January 2015 and 31 December 2019 (64 patients, 53.1% males, aged 70.88 ± 16.44 years). All patients underwent a complete physical examination, pulmonary computerised tomography, laboratory tests, D-dimers and blood gas analysis at the time of diagnosis. RESULTS: There were no differences in laboratory tests nor in D-dimers between the two groups. In the CPE group we found a significantly increased pO2 (92.83 ± 42.52 vs. 76.11 ± 32.58 mmHg; p < 0.05), difference of oxygen between alveoli and arteries (A-aDO2; 169.3 ± 171.9 vs. 52.97 ± 39.65 mmHg; p < 0.05), and oxygen saturation % (97.06 ± 2.59 vs. 93.77 ± 5.53%; p < 0.05) compared to controls. No difference was found in pCO2 and the ratio between pO2 and percentage of inspired oxygen (P/F). Finally, a significantly decreased urate (3.67 ± 1.49 vs. 5.60 ± 2.10; p < 0.05) was found in CPE compared to controls. In CPE, platelets count presents an inverse correlation to P/F (r = -0.389, p = 0.02) but a direct correlation to A-aDO2 (r = 0.699, p = 0.001). No similar findings were present in controls. DISCUSSION: COVID-19 PE appears to have a different clinical setting. Reduced oxygenation described in PE may not to be considered as a sign of disease. The increased A-aDO2 may indicate that COVID-19 PE involved smaller vessels compared to classical PE. A possible diffuse capillary thrombosis could explain these results.

Cardiovascular Risk Score and Pulmonary Gas Exchange in COVID-19 Patients Show No Correlation.

BACKGROUND: COVID-19 induces robust systemic inflammation. Patients with cardiovascular disease (CVD) are at an increased risk of death. However, much effort is being spent to identify possible predictors of negative outcomes in order to have a more specific clinical setting. CVD scores are a useful tool in evaluating risk of cardiovascular events. AIM: We evaluated oxygenation and characteristics in COVID-19 patients according to cardiovascular risk stratification performed using the Framingham risk score (FRS) for cardiovascular disease. MATERIALS AND METHODS: We evaluated 155 COVID-19 patients (110 males and 45 females, aged 67.43 ± 14.72 years). All patients underwent a complete physical examination, chest imaging, laboratory tests and blood gas analysis at the time of diagnosis. Seventeen patients died (10 males and 7 females, aged 74.71 ± 7.23 years) while the remaining 138 patients (100 males and 38 females, aged 66.07 ± 15.16 years) were alive at discharge. RESULTS: Deceased patients have an increased FRS compared to those that survived (27.37 ± 5.03 vs. 21.33 ± 9.49, p < 0.05). Compared to survivors, the deceased group presents with a significant increase in white blood cells (p < 0.05) and D-dimers (p < 0.05). There was no difference in pCO2, SO2, and in alveolar arteriolar oxygen difference (A-aDO2). On the contrary, in deceased patients there was an increased pO2 (p < 0.05) and a decreased ratio between oxygen inspired and pO2 (P/F; p < 0.05). FRS shows a negative correlation to P/F (r = 0.42, p < 0.05) in the deceased while no correlation was found in the survivors. No other correlation has been found with blood gas parameters or in the inflammation parameters evaluated in the two groups. DISCUSSION: CVD may be considered as a major risk factor for death in COVID-19 patients. The increased risk relates to a reduced lung capacity but it is not related to blood gas values. Similarly, CV risk score results are independent from the inflammatory status of the patients.

Tissue and circulating microRNAs as biomarkers of response to obesity treatment strategies.

BACKGROUND: Obesity, characterized by an increased amount of adipose tissue, is a metabolic chronic alteration which has reached pandemic proportion. Lifestyle changes are the first line therapy for obesity and a large variety of dietary approaches have demonstrated efficacy in promoting weight loss and improving obesity-related metabolic alterations. Besides diet and physical activity, bariatric surgery might be an effective therapeutic strategy for morbid obese patients. Response to weight-loss interventions is characterised by high inter-individual variability, which might involve epigenetic factors. microRNAs have critical roles in metabolic processes and their dysregulated expression has been reported in obesity. AIM: The aim of this review is to provide a comprehensive overview of current studies evaluating changes in microRNA expression in obese patients undergoing lifestyle interventions or bariatric surgery. RESULTS: A considerable number of studies have reported a differential expression of circulating microRNAs before and after various dietary and bariatric surgery approaches, identifying several candidate biomarkers of response to weight loss. Significant changes in microRNA expression have been observed at a tissue level as well, with entirely different patterns between visceral and subcutaneous adipose tissue. Interestingly, relevant differences in microRNA expression have emerged between responders and non-responders to dietary or surgical interventions. A wide variety of dysregulated microRNA target pathways have also been identified, helping to understand the pathophysiological mechanisms underlying obesity and obesity-related metabolic diseases. CONCLUSIONS: Although further research is needed to draw firm conclusions, there is increasing evidence about microRNAs as potential biomarkers for weight loss and response to intervention strategies in obesity.

Molecular Mechanisms of Notch Signaling in Lymphoid Cell Lineages Development: NF-κB and Beyond.

Notch is a ligand-receptor interaction-triggered signaling cascade highly conserved, that influences multiple lineage decisions within the hematopoietic and the immune system. It is a recognized model of intercellular communication that plays an essential role in embryonic as well as in adult immune cell development and homeostasis. Four members belong to the family of Notch receptors (Notch1-4), and each of them plays nonredundant functions at several developmental stages. Canonical and noncanonical pathways of Notch signaling are multifaceted drivers of immune cells biology. In fact, increasing evidence highlighted Notch as an important modulator of immune responses, also in cancer microenvironment. In these contexts, multiple transduction signals, including canonical and alternative NF-κB pathways, play a relevant role. In this chapter, we will first describe the critical role of Notch and NF-κB signals in lymphoid lineages developing in thymus: natural killer T cells, thymocytes, and thymic T regulatory cells. We will address also the role played by ligand expressing cells. Given the importance of Notch/NF-κB cross talk, its role in T-cell leukemia development and progression will be discussed.

Belimumab restores Treg/Th17 balance in patients with refractory systemic lupus erythematosus.

Belimumab, a specific inhibitor of the soluble B lymphocyte stimulator (BlyS), is the first biological drug approved by the United States Food and Drug Administration for the treatment of patients with active systemic lupus erythematosus (SLE) refractory to standard therapy. Given that an imbalance between regulatory T cells (Treg) and interleukin (IL)-17A-secreting T cells (Th17) has been reported in various autoimmune disorders, we assessed the frequency of both Treg and Th17 peripheral blood populations before and after belimumab administration in 20 patients with active SLE refractory to standard therapy. After six months of treatment, the mean SELENA-SLEDAI score as well as the mean anti-double-stranded DNA antibody titers were significantly decreased. In addition, we observed a significant increase in Treg percentages and a parallel, significant decrease in Th17 percentages, accompanied by significantly reduced serum levels of IL-21. In vitro studies showed that Treg purified from belimumab-treated patients were fully functional and displayed a suppressor function similar to that of Treg purified from healthy donors. Belimumab can restore Treg/Th17 balance in SLE patients with uncontrolled disease activity, and this results in decreased flare rate and reduced glucocorticoid dosage.

Mucine-1 Is Related to Cell-Mediated Immunoexpression and Blood Pressure in Pulmonary Artery in Pulmonary Arterial Hypertension (PAH): Preliminary Results.

BACKGROUND AND AIM: Mucine-1 (MUC1) increases in primary lung disease; however, no data are available on pulmonary arterial hypertension (PAH). Our aim was to analyze MUC1 in PAH and a possible link with pulmonary artery pressure (PAPs), PaO2, PaCO2 and cell-mediated immunity. METHODS: We studied nine PAH patients (four males and five females, aged 52 ± 21 years). The control groups were nine patients with pulmonary hypertensions due to lung disease (PPH; five males and four females, aged 63 ± 18 years) and 14 patients with left heart disease (HPH; four males and ten females, aged 73 ± 13 years). All underwent arterial gas analysis and echocardiography. A serum sample was collected to determine MUC1 and CD40L values on ELISA. RESULTS: No differences were found for PAPs and CD40L. MUC1 resulted in comparable values between PAH and HPH but decreased when compared to PPH (16.46 ± 4.12 vs 116.6 ± 47.08 U/ml, p = 0.049). pO2 was higher in PAH (PAH 83.18 ± 1.77 vs PPH 62.75 ± 3.23 mmHg, p = 0.003; vs HPH 65.83 ± 6.94 mmHg, p = 0.036). pCO2 was lower compared to PPH (36.15 ± 2.19 vs 45.83 ± 3.00 mmHg, p = 0.026) but not compared to HPH. In PAH patients the MUC1 correlated with pO2 (r = -0.91), pCO2 (r = 0.80), PAPs (r = 0.82) and CD40L (r = 0.72) while it did not in PPH and HPH. CONCLUSIONS: These preliminary data show a possible mechanism of immune stimulation in PAH patients. This may imply an association between lung parenchyma, immunity and increase in vascular resistance. Additional studies are required to confirm these findings.

Analysis of Aortic Remodeling and Stiffness in Patients with Obstructive Sleep Apnea Syndrome: Preliminary Results.

Obstructive sleep apnea (OSA) is a well-known risk factor for cardiovascular diseases. Several studies have shown that OSA is associated with vessel remodeling, but few studies have examined aorta. AIM: to analyse aortic remodelling in OSA. METHODS: Thirty consecutive OSA patients (22 males and 8 females, aged 58.5 ± 13.2 years) were studied. All patients underwent a morning blood gas analysis, a full cardiorespiratory evaluation, including nocturnal polygraphy and echocardiography, that assessed aortic root diameter (ARD) and aortic stiffness index (ASI). Patients were grouped as follows: Group 1, non-severe OSA (Apnea-Hypopnea Index; AHI <30, 14 patients); Group 2, severe OSA (AHI ≥30, 16 patients). RESULTS: No difference was found between the groups in ARD as absolute value (Group 1, 33.64 ± 0.91 mm; Group 2, 33.64 ± 1.02, p = ns) and as normalized value for the body surface area - ARDi (Group 1, 16.72 ± 0.63 mm/m2; Group 2, 16.09 ± 0.44, p = ns). Moreover, no difference was found in the ASI (Group 1, 14.04 ± 2.26; Group 2, 13.41 ± 2.22, p = ns). Considering all OSA patients, AHI showed an inverse correlation with ARDi (p = 0.018) and ASI (p = 0.0449). Moreover, the ASI showed a direct correlation with ARDi (p = 0.01) and morning PaO2 (p = 0.0349) as well as an inverse correlation with the oxygen desaturation index (ODI, p = 0.031) and total time with apnea and hypopnea (p = 0.039). CONCLUSION: No difference was found between severe and non-severe OSA in ARD. Surprisingly, the data show that the severity of OSA correlates inversely with the ASI and ARDi. The relation between PaO2 and stiffness might be explained by a feedback mechanism that tries to overcome the reduction of aortic elasticity due to night desaturation. These findings need to be investigated in further studies with a larger study population.

Safe fluoroquinolones prophylaxis in blood cancer patients with chemotherapy-induced neutropenia and Glucose-6-Phosphate-Dehydrogenase deficiency.

WHAT IS KNOWN AND OBJECTIVE: Bacterial infections are the leading causes of morbidity and mortality in haematologic patients with chemotherapy-induced neutropenia. The only strategy shown to be effective in reducing febrile neutropenia incidence is fluoroquinolone prophylaxis, but the safety of this class of drugs in patients with glucose-6-phosphate dehydrogenase deficiency (G6PD-), the most common human enzyme defect, is still controversial because of the claimed association with acute haemolytic anaemia. METHODS: We retrospectively analysed 242 patients treated with 628 intensive chemotherapy courses. Of these, 59 patients were with G6PD-. All patients underwent fluoroquinolone prophylaxis and were transfused according to our single-unit transfusion policy. The principal endpoint was the incidence of acute haemolytic anaemia. Secondary endpoints included the incidence of febrile neutropenia, microbiologically and clinically documented infection (MDI and CDI) and the incidence of Gram-positive or Gram-negative infections. RESULTS AND DISCUSSIONS: No episode of acute haemolytic anaemia was observed in the entire cohort. The incidence of MDI and CDI was similar, but the incidence of invasive fungal disease (IFD; P<.0001, HR 11.4, 95%CI 3.5-37.05) and Candida sepsis (P=.008, HR 37, 95%CI 2.01-680.9) was higher in patients with G6PD-. Interestingly, we observed a reduced incidence of febrile neutropenia in patients with G6PD- (P=.01, HR 0.46, 95%CI 0.25-0.8). WHAT IS NEW AND CONCLUSIONS: Our data suggest that fluoroquinolone prophylaxis in patients with G6PD-, treated with intensive chemotherapy, is feasible and safe. Our findings on the incidence of IFD and febrile neutropenia suggest that G6PD may be important in susceptibility to opportunistic pathogens and host response in neutropenic patients.

Probiotics and refractory chronic spontaneous urticaria.

Background. In chronic spontaneous urticaria (CSU) first-line therapy with an antihistamine-based regimen may not achieve satisfactory control in patients. Thus, a continuing need exists for effective and safe treatments for refractory CSU. Aim. To evaluate the clinical efficacy and safety of an intake of a combination of 2 probiotics (Lactobacillus salivarius LS01 and Bifidobacterium breve BR03) in patients with CSU who remain symptomatic despite concomitant H1-antihistamine therapy. Methods. This report analyzes the effects of therapy with two probiotic strains on the clinical progress of 52 unselected patients with difficulty to treat CSU underwent to medical examination in two Italian specialist urticaria Clinics between September 2013 and September 2014. A mixture of Lactobacillus LS01 and Bifidobacterium BR03 were administered in each patient twice daily for 8 weeks. To evaluate patients' improvement with probiotics, urticaria activity score over 7 days (UAS7) was used at baseline and at week 8 in addition to a 5-question urticaria quality of life questionnaire. Results. Fifty-two patients with CSU were included in this study (10 male and 42 female, age range 19-72 years). Mean disease duration was 1.5 years. Fourteen patients discontinued treatment, so evaluable population consisted of 38 patients. Nine of the 38 patients experienced mild clinical improvement during probiotic treatment (23.7%); one patient reported significant clinical improvement (2.6%) and one patient had complete remission of urticaria (2.6%). Twenty-seven patients did not have improvement in symptoms (71.1%). No side effects during the course of therapy were reported. Conclusions. A combination of Lactobacillus salivarius LS01 and Bifidobacterium breve BR03 administered twice daily for 8 weeks might reduce the symptoms scores and improve quality of life scores in a part of patients with CSU who remained symptomatic despite treatment with H1 antihistamine mostly in subjects with allergic rhinitis.

Immediate-type hypersensitivity reaction to Mannitol as drug excipient (E421): a case report.

Allergic reactions to mannitol have been reported rarely, despite its widespread use as a drug and as a food excipient. This is the first case report in which oral mannitol induces an immediate type hypersensitivity as a drug excipient, in a 42 year old man affected by rhinitis to olive tree pollen. Unusual and undervalued risk factors for mannitol hypersensitivity are examined.

Severe pulmonary hypertension as the initial manifestation of systemic lupus erythematosus: a case report and review of the literature.

Severe pulmonary arterial hypertension (PAH) is rarely observed as the initial manifestation of systemic lupus erythematosus (SLE), and the diagnosis is often delayed. Here we present the case of a 32-year-old woman with severe PAH as the initial manifestation of SLE, who was successfully treated with mycophenolate mofetil and cyclosporine. This case offered the opportunity to critically review the epidemiology data, predictive markers, and pathogenic pathways of SLE-associated PAH (SLE-PAH) in relation to the currently available therapeutic options and to the main clinical trials of the last 10 years focused on the treatment of SLE-PAH. Mycophenolate mofetil and cyclosporine - currently used in the maintenance phase of the disease in certain clinical settings - should be considered, as an alternative to cyclophosphamide, in future clinical trials aimed at evaluating the most effective treatment of SLE-PAH at presentation.

Molecular diagnosis and the Italian Board for ISAC.

The Component Resolved Diagnostic (CRD) approach has been developed when highly purified or recombinant allergen molecules have become available. These molecules are the allergenic proteins toward which the specific and clinically relevant IgE immune response is directed. So, the identification of protein families and cross-reactivity patterns of importance in allergy have been possible. The Italian advisory BOARD for ISAC was born: to evaluate the advantages, disadvantages and placement in diagnosis of CRD studying its application in allergic patients; to facilitate the interpretation of molecular diagnostics for clinical allergists; to evaluate the effectiveness of CRD in improving diagnostic risk assessment and early preventive treatment of allergic diseases. In the last years, its fields of interest have been: the evaluation of the performance of CRD on multi-sensitized allergic patients with respiratory symptoms and on poly-sensitized athletes; the evolution of IgE repertoire directed to single allergenic components by evaluating allergic patients with different age at a molecular level; the relevance of results obtained using allergen microarray technique for describing the IgE repertoire in allergic patients by reviewing the main articles focused on CRD published in the last 2 years; the need for an educational program focused on this new diagnostic tool also through the creation of an exhaustive and interactive explanation of the laboratory report molecular allergy; the investigation of the performance and potential additional diagnostic values of the ISAC microarray in a real-life clinical setting, taking into account also the economic values.

A GIS based method for soil mapping in Sardinia, Italy: a geomatic approach.

A new project was recently initiated for the realization of the "Land Unit and Soil Capability Map of Sardinia" at a scale of 1:50,000 to support land use planning. In this study, we outline the general structure of the project and the methods used in the activities that have been thus far conducted. A GIS approach was used. We used the soil-landscape paradigm for the prediction of soil classes and their spatial distribution or the prediction of soil properties based on landscape features. The work is divided into two main phases. In the first phase, the available digital data on land cover, geology and topography were processed and classified according to their influence on weathering processes and soil properties. The methods used in the interpretation are based on consolidated and generalized knowledge about the influence of geology, topography and land cover on soil properties. The existing soil data (areal and point data) were collected, reviewed, validated and standardized according to international and national guidelines. Point data considered to be usable were input into a specific database created for the project. Using expert interpretation, all digital data were merged to produce a first draft of the Land Unit Map. During the second phase, this map will be implemented with the existing soil data and verified in the field if also needed with new soil data collection, and the final Land Unit Map will be produced. The Land Unit and Soil Capability Map will be produced by classifying the land units using a reference matching table of land capability classes created for this project.

Surviving adversity: Exploring the presence of Lunularia cruciata (L.) Dum. on metal-polluted mining waste.

The tailings dump of Barraxiutta (Sardinia, Italy) contains considerable concentrations of heavy metals and, consequently, is scarcely colonized by plants. However, wild populations of the liverwort Lunularia cruciata (L.) Dum. form dense and healthy-looking carpets on this tailing dump. L. cruciata colonizing the tailing dump was compared with a control population growing in a pristine environment in terms of: (i) pollutant content, (ii) photochemical efficiency, and (iii) volatile secondary metabolites in thalli extracts. L. cruciata maintained optimal photosynthesis despite containing considerable amounts of soil pollutants in its thalli and had higher sesquiterpene content compared to control plants. Sesquiterpenes have a role in plant stress resistance and adaptation to adverse environments. In the present study, we propose enhanced sesquiterpenes featuring Contaminated L. cruciata as a defence strategy implemented in the post-mining environment.

The additional values of microarray allergen assay in the management of polysensitized patients with respiratory allergy.

BACKGROUND: The IgE response is directed against specific components from an allergenic source. The traditional diagnostic methods use whole extracts, containing allergenic, nonallergenic and cross-reactive molecules. This may pose diagnostic challenges in polysensitized patients. Microarray techniques detect specific IgE against multiple molecules, but their value in term of additional information and economic saving has not been yet defined. OBJECTIVE: We assessed the additional diagnostic information provided by an allergen microarray in a large population of polysensitized subjects. METHODS: In this multicentre study, allergists were required to carefully record diagnosis and treatment of consecutive patients referred for asthma/rhinitis, using the standard methodology (history, skin prick test, IgE assay). Then, a microarray allergen assay was carried out. Clinicians were required to review their diagnosis/treatment according to microarray results. RESULTS: 318 allergic patients (30% reporting also nonrespiratory symptoms) and 91 controls were enrolled. The clinicians reported at least one additional information from the microarray in about 60% of patients, this resulting in therapeutic adjustments. In 66% of patients IgE to pan-allergens were detectable, being this clinically relevant in 38% of patients with polysensitization to pollens. CONCLUSION: Microarray IgE assay represents an advancement in allergy diagnosis, as a third-level approach in polysensitized subjects, when the traditional diagnosis may be problematic.

Rituximab treatment for 'rhupus syndrome': clinical and power-Doppler ultrasonographic monitoring of response. A longitudinal pilot study.

OBJECTIVE: To evaluate the safety and efficacy of rituximab in patients suffering from rhupus unresponsive to therapy with non-biological disease-modifying anti-rheumatic drugs (DMARDs). METHODS: Six patients fulfilling criteria for both rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) and with a DAS28 score >5.1 were enrolled to receive two fortnightly 1000 mg rituximab doses at baseline and after 28 weeks. All patients underwent clinical, laboratory, and power- Doppler (PD) ultrasonographic (US) assessment at baseline and after 14, 28 and 56 weeks. RESULTS: A sustained improvement in DAS28, SLEDAI, HAQ, laboratory markers and ultrasound indices together with a significant reduction in the daily dose of prednisone were observed throughout follow-up. CONCLUSION: Rituximab may be a safe and effective therapeutic option in refractory rhupus patients.

Short-term tolerability of morniflumate in patients with cutaneous hypersensitivity reactions to non-steroidal anti-inflammatory drugs.

Morniflumate is the morpholinoethyl ester of niflumic acid, a non-steroidal anti-inflammatory drug, derived from nicotinic acid. We studied 112 patients who had experienced cutaneous reactions after using non-steroidal anti-inflammatory drugs. Only two of all the patients who underwent an oral challenge with morniflumate had a positive result to the test. By demonstrating the low incidence of reactions to morniflumate through oral challenges, we suggest that patients with non-steroidal anti-inflammatory drug hypersensitivity may tolerate this drug which would therefore be a useful alternative.

Non-invasive investigation of Spironucleus vortens transmission in freshwater angelfish Pterophyllum scalare.

Spironucleus vortens is a protozoan fish parasite of veterinary and economic importance in the ornamental aquaculture industry. Despite this, key aspects of the life cycle of this organism, including its mode of transmission, have not been fully elucidated. We developed a non-invasive method for quantifying S. vortens in freshwater angelfish, which was then used to investigate parasite transmission and aggregation within host populations. As previously observed for S. meleagridis and S. salmonis, motile S. vortens trophozoites were detected in host faeces using light microscopy. Species-level identification of these flagellates was confirmed using 16S rDNA PCR. Faecal trophozoite counts were significantly correlated with trophozoite counts from the posterior intestine, the primary habitat of the parasite. This novel finding allowed effective prediction of intestinal parasite load from faecal counts. Overall, faecal count data revealed that 20% of hosts harbour 83% of parasites, conforming to the Pareto Principle (80/20 rule) of parasite aggregation with implications for parasite transmission. Trophozoites survived for ≥36 d outside the host within faeces and remained motile at low pH (comparable with that of angelfish stomach). No putative S. vortens cysts were observed in cultures or faecal samples. This calls into question the commonly accepted hypothesis that a protective cyst is required in the life cycle of S. vortens to facilitate transmission to a new host.

Diagnosis of latex allergy: the importance of hev B 11.

We present the cases of 5 patients with a positive clinical history of cutaneous symptoms due to contact with latex products. A latex allergological assessment was made through skin prick tests (SPTs) both with commercial latex extracts and extemporaneous glove extracts, and serum-specific IgE to latex and glove-use tests. In addition, serum-specific IgE to recombinant allergens for Hevea brasiliensis was dosed. Molecular diagnostics in association with the glove-use test and, to a lesser extent, the SPTs with glove eluate are useful diagnostic tests to confirm the diagnosis of latex allergy in patients with mucocutaneous symptoms.

Susceptibility to ankylosing spondylitis but not disease outcome is influenced by the level of HLA-B27 expression, which shows moderate variability over time.

OBJECTIVE: Previous reports have highlighted the relevance of HLA-B27 expression in the pathogenesis of ankylosing spondylitis (AS). The aim of the current study was to estimate the level of HLA-B27 expression on the cell surface of ex vivo monocytes and lymphocytes by a quantitative method and to correlate this with AS disease susceptibility, disease clinical indexes, and the occurrence of acute anterior uveitis (AAU). METHOD: We recruited 32 B27-positive patients with AS and 32 B27-positive healthy normal controls (NCs) for evaluation at different time points. The expression of HLA-B27 molecules was quantified by flow cytometry on ex vivo peripheral blood mononuclear cells (PBMCs). Patients were also evaluated by scores on the Bath AS disease activity (BASDAI), functional (BASFI), and metrology (BASMI) indexes. RESULTS: The expression of HLA-B27 molecules was significantly higher in patients with AS than in B27-matched controls in the case of both monocytes [219K (IQR 174K-308K) vs. 137K (IQR 96K-170K), p < 0.0001] and lymphocytes [82K (IQR 58K-118K) vs. 54K (IQR 44K-61K), p < 0.0001]; AS only vs. AS with AAU: p = 0.744 in monocytes and p = 0.701 in lymphocytes. Comparisons with metrology and functional indexes were also not significant (BASMI: r = 0.05, p = 0.77; BASFI: r = -0.09, p = 0.67). The overexpression of HLA-B27 molecules was stable after 1 week of follow-up. At 3 years follow-up, the variability was moderate and did not correlate with variations in disease activity (BASDAI: r = -0.01, p = 0.92 ns). CONCLUSIONS: The level of HLA-B27 expression in PBMCs correlates with the susceptibility to AS but not with the disease outcome, nor with the occurrence of extra-articular manifestations such as AAU.