Effects of intrauterine device use on attack frequency and severity in woman of reproductive age with familial Mediterranean fever.

AIM: Familial Mediterranean fever (FMF) is the most common inherited autoinflammatory disease in the world. There are known triggers to initiate an FMF attack, yet potential effects of intrauterine devices (IUD) in women of reproductive age have not been evaluated before. METHOD: Consecutive female patients with FMF who ever used IUD over the age of 18 were enrolled. Female patients with FMF were sub grouped according to the type of IUD they use. FMF attack frequency, severity, duration, presence of dysmenorrhea, severity of dysmenorrhea, having attacks during menstruation before and after IUD use were questioned. Demographic and clinical data were collected from hospital database. RESULTS: When all patients with IUD use were evaluated, it was found that the frequency of attacks increased after IUD insertion at 3rd and 12th months (median [min-max] attack frequency at 3rd month, 1 (0-3) vs 1 (0-6), p = 0.002, median [min-max] attack frequency at 12th month, 2 (0-12) vs 3.5 (0-18), p = 0.028). Attack severity measured by VAS pain was also significantly increased. Attack duration and menstrual pain was similar before and after IUD use. Attack frequency at 3rd and 12th months, attack severity and menstrual pain was all increased significantly in Cu-IUD users, whereas none of these parameters deteriorated in LNG-IUD group. CONCLUSION: IUD use, especially Cu-IUD, may increase the frequency and severity of attacks in female patients with FMF. Clinicians may benefit from considering LGN-IUD if IUDs are preferred as contraception in women of childbearing age with FMF.

Effects of sulfasalazine in axial spondyloarthritis on COVID-19 outcomes: real-life data from a single center.

INTRODUCTION: Compared to biological agents, little is known about the impact of sulfasalazine therapy on COVID-19 outcomes in patients with Axial Spondyloarthritis (AxSpA). Therefore, we aimed to evaluate the COVID-19 severity in AxSpAs receiving sulfasalazine and biologic-agent. MATERIALS AND METHODS: A total of 219 SARS-CoV-2 positive AxSpA patients were retrospectively analyzed. COVID-19 pneumonia, hospitalization rate, and length of stay were used to determine COVID-19 severity. AxSpA patients were mainly grouped and compared as sulfasalazine and non-sulfasalazine. Afterward, we excluded no-treatment patients to reveal the drug's effects more clearly and regrouped AxSpA patients as sulfasalazine-monotherapy (34.3%), biologic-monotherapy (33.7%), and sulfasalazine + biologic (7.3%). RESULTS: Fifty-nine percent of the patients were male and the mean age was 45.0 years. Peripheral arthritis was 35% and uveitis 15%. In total, 41.5% of them have received sulfasalazine and 41.0% biologic agents, and the remaining patients with no AxSpA-specific treatment. In the first comparison, the sulfasalazine group had a higher age, more frequent COVID-19 pneumonia, hospitalization, and longer hospitalization than a non-sulfasalazine group. In the pairwise comparison of 3 treatment groups, the demographic and clinical features, the hospitalization rate and the length of hospital stay were similar but the sulfasalazine-monotherapy group had a higher frequency of COVID-19 pneumonia than the biologic-monotherapy group (23% vs. 7%, p = 0.008). CONCLUSION: Our results imply sulfasalazine may be related to more severe COVID-19 in AxSpA patients. These patients should be followed more carefully in the presence of COVID-19, regardless of reasons such as age, comorbidity, and extra-axial disease, and consideration of discontinuing sulfasalazine maybe even thought.

Dynamic thiol-disulfide homeostasis as an oxidative stress marker in ankylosing spondylitis and undifferentiated spondyloarthropathy.

Background/aim: Seronegative spondyloarthropathies (SpA) are a group of chronic diseases characterized by axial inflammation, oligoarthritis, and enthesitis. Oxidative stress may contribute to a wide range of rheumatologic diseases, including SpA. This prospective case-control study was designed to compare thiol-disulfide levels as a marker of oxidative stress between SpA patients and healthy controls. Materials and methods: A total of 144 patients diagnosed with undifferentiated spondyloarthropathy (USpA, n = 97) or ankylosing spondylitis (AS, n = 47) were included along with 80 healthy controls. Serum native thiol (NT), total thiol (TT), and disulfide (D) levels were measured using the fully automated Erel method. The ratios NT/TT, D/TT, and D/NT were calculated. Thiol-disulfide levels were compared between the SpA groups and the healthy controls. Results: The NT and NT/TT ratios were found to be significantly lower in the SpA group (p < 0.001). The disulfide, D/NT, and D/TT ratios were found to be significantly higher in the SpA group (p < 0.001). In pairwise comparisons between the SpA subgroups, the NT and TT levels were lower in the USpA group than in the AS group (p = 0.021), but serum disulfide levels were higher in the USpA group than in the AS group (p = 0.004). Among the patients with SpA, the group taking antitumor necrosis factor (anti-TNF) had lower TT measurements compared to the group taking conventional disease modifying antirheumatic drugs (DMARD) (p = 0.039). Conclusion: The thiol-disulfide balance is disturbed in favor of disulfide in SpA patients compared to healthy volunteers. Native and total thiol measurements correlate with acute phase reactants and might be used to monitor disease activity. Anti-TNF therapy might control the oxidative degenerative process better than the conventional DMARD in SpA patients.

The effectiveness of anti-interleukin-1 therapy on subclinical inflammation parameters during the attack-free period in familial Mediterranean fever patients: A case-control study.

BACKGROUND: : Anti IL-1 therapy is useful in suppressing attacks in FMF patients with colchicine resistance, however, it is not certain whether subclinical inflammation can sufficiently be inhibited with anti-IL-1 therapy in FMF patients with amyloidosis. METHODS: Forty-six FMF patients receiving anti-interleukin-1 therapy and 36 healthy control patients were compared in terms of laboratory parameters. Also, FMF patients were further divided into two groups; those with amyloidosis and those without it, and these subgroups were compared to each other in terms of clinical and laboratory findings. RESULTS: In comparison between the FMF and healthy control groups, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) level, and red cell distribution width (RDW) level were detected to be higher and hemoglobin level lower in the patient group. Within the FMF patient group, the ESR, CRP, fibrinogen, RDW, and NLR values were significantly higher in the subgroup with amyloidosis in comparison to the subgroup without amyloidosis. DISCUSSION: Anti-interleukin-1 therapy could not fully suppress the subclinical inflammatory parameters when compared to healthy individuals.

The effectiveness of anti-interleukin-1 therapy on subclinical inflammation parameters during the attack-free period in familial Mediterranean fever patients: A case-control study.

Background/aim: Anti IL-1 therapy is useful in suppressing attacks in FMF patients with colchicine resistance, however, it is not certain whether subclinical inflammation can sufficiently be inhibited with anti-IL-1 therapy in FMF patients with amyloidosis. Materials and methods: Forty-six FMF patients receiving anti-interleukin-1 therapy and 36 healthy control patients were compared in terms of laboratory parameters. Also, FMF patients were further divided into two groups; those with amyloidosis and those without it, and these subgroups were compared to each other in terms of clinical and laboratory findings. Results: In comparison between the FMF and healthy control groups, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) level, and red cell distribution width (RDW) level were detected to be higher and hemoglobin level lower in the patient group. Within the FMF patient group, the ESR, CRP, fibrinogen, RDW, and NLR values were significantly higher in the subgroup with amyloidosis in comparison to the subgroup without amyloidosis. Conclusion: Anti-interleukin-1 therapy could not fully suppress the subclinical inflammatory parameters when compared to healthy individuals.

Multiple layers of B cell memory with different effector functions.

Memory B cells are at the center of longstanding controversies regarding the presence of antigen for their survival and their re-engagement in germinal centers after secondary challenge. Using a new mouse model of memory B cell labeling dependent on the cytidine deaminase AID, we show that after immunization with a particulate antigen, B cell memory appeared in several subsets, comprising clusters of immunoglobulin M-positive (IgM(+)) and IgG1(+) B cells in germinal center-like structures that persisted up to 8 months after immunization, as well as IgM(+) and IgG1(+) B cells with a memory phenotype outside of B cell follicles. After challenge, the IgG subset differentiated into plasmocytes, whereas the IgM subset reinitiated a germinal center reaction. This model, in which B cell memory appears in several layers with different functions, reconciles previous conflicting propositions.

Dynamic Thiol/Disulphide Homeostasis as Oxidative Stress Marker in Ankylosing Spondylitis and Undifferentiated Spondyloarthropathy.

AIM: Seronegative spondyloarthropathies (SpA) are a group of chronic diseases, characterized by axial inflammation, oligoarthritis, and enthesitis. Oxidative stress may contribute to a wide range of diseases such as rheumatologic diseases including SpA. This prospective case-control study was designed to compare the thiol-disulfide levels as a marker of oxidative stress in SpA patients with healthy controls. METHODS: A total of 144 patients who were diagnosed as undifferentiated spondyloarthropathy (UspA, n=97), ankylosing spondylitis (AS, n=47), and 80 healthy controls were included. Serum native thiol (NT), total thiol (TT), disulfide (D) levels were measured with the fully automated Erel?s method. NT/TT, D/TT, and D/NT ratios were calculated. Thiol-disulfide levels were compared between SpA groups and healthy controls. RESULTS: NT and NT/TT ratios were found to be significantly lower in the SpA group. (p<0.001). Disulfide, D/NT, and D/TT ratios were found to be significantly higher in the SpA group (p <0.001 for each comparison). In pairwise comparisons between SpA subgroups, NT and TT levels were lower in USpA group compared to AS group (P=0.021). Serum disulfide levels were higher in USpA group compared to AS group (P=0,004). Anti-tumor necrosis factor (Anti-TNF) group had lower TT measurements compared to the classical disease-modifying anti-rheumatic drugs (cDMARD) group in patients with SpA (P=0.039). CONCLUSION: Thiol-disulfide balance is disturbed in favor of disulfide in SpAs patients compared to healthy volunteers. Native and total thiol measurements correlate with acute phase reactants and might be used to monitor disease activity. Anti-TNF therapy might control the oxidative degenerative process better than the classical DMARD in SpA patients.

Avascular necrosis less frequently found in systemic lupus erythematosus patients with the use of alternate day corticosteroid

Background/aim: Avascular necrosis (AVN) is the death of bone due to compromise of blood flow. The etiology of AVN is multifactorial; corticosteroid usage is the second most significant factor after trauma, and systemic lupus erythematosus (SLE) is the most common underlying disease. The objective of this study was to assess the factors of AVN in SLE patients. Materials and methods: The study included 127 patients with SLE who fulfilled 1997 American College of Rheumatology (ACR) revised criteria. Demographic data, age at SLE diagnosis, disease duration, disease activity, body mass index, clinical findings, antiphospholipid syndrome, steroid usage, dose and duration, comorbid diseases, and smoking history were recorded. Results: AVN was found in 11 of 127 (8.7%) SLE patients. Hyperlipidemia (P < 0.001), cushingoid body habitus (P < 0.001), and proteinuria (P = 0.013) were found at higher rates in the AVN group. All of the 11 AVN cases had osteoporosis (P < 0.02). In multivariate regression analysis, daily steroid usage was the only factor for development of AVN in SLE. Conclusion: The hypothesis of our study was that an alternate day steroid regimen may decrease AVN frequency in SLE patients.

Evaluation of auditory and cochlear functions in ankylosing spondylitis patients according to the site of involvement.

Ankylosing spondylitis (AS) is a chronic systemic inflammatory disease of unknown origin with a prevalence rate about 1% in the population. Audiovestibular dysfunction is encountered in AS and sensorineural hearing loss is the most common form. The present study aimed to evaluate auditory and cochlear function in AS patients according to the site of involvement. A total of 47 patients followed for AS in the rheumatology outpatient clinic and 30 healthy controls were enrolled in the study. Subgroups of AS were identified according to the site of involvement. The participants underwent complete otolaryngological examination together with audiometry, otoacoustic emission and tympanometry tests. Disease Activity Index (BASDAI) was determined in the AS group. Hearing loss was detected in seven patients (15%) in the AS group and in four subjects (8%) in the control group. There was statistically significant difference between the patient and control groups in terms of mean bone conduction hearing level at 4000 hertz (Hz) in the right and left ears (p = 0.028, p = 0.049). There was no significant difference between the subgroups of AS in terms of overall auditory and cochlear functions. No correlation was determined between auditory values and Disease Activity Index and CRP (p > 0.05 for all). Our results reveal that AS has minimal effect on auditory and cochlear functions. The effects of subgroups of AS on auditory functions were comparable. The authors concluded that BASDAI and CRP are not convenient in monitoring auditory functions of AS patients.

Efficacy of golimumab on recurrent uveitis in HLA-B27-positive ankylosing spondylitis.

To evaluate the efficacy of golimumab on severe and frequent recurrent anterior uveitis in patients with HLA-B27-positive ankylosing spondylitis. In this study, 15 eyes of 12 HLA-B27-positive AS patients with resistant anterior uveitis who received 50 mg of subcutaneous golimumab (Gol) per month due to frequent uveitis recurrences were analyzed retrospectively between May 2013 and October 2015. Assessment criteria were uveitis activity, the number of recurrence of uveitis, visual acuity, systemic corticosteroid, or other drug requirement for maintenance of remission of AU. Twelve patients (15 eyes) with HLA-B27-positive ankylosing spondylitis and anterior uveitis have been treated with golimumab 50 mg/month. Remission of uveitis was observed in 12 eyes out of 15. Malign hypertension developed in one subject after the second dose of golimumab therefore the treatment was stopped and this subject was excluded from the study. Median follow-up time was 11 months (interquartile range: 8-18). No uveitic reaction was seen except in the patient who stopped treatment. No topical or systemic steroid necessity was needed except in two cases with oral 4 mg systemic maintenance. Visual acuity was significantly increased (p = 0.002). Golimumab may be a new and effective choice for maintaining remission and the prevention of recurrences of severe, resistant anterior uveitis in patients with HLA-B27-positive ankylosing spondylitis.

Effect of capillaroscopic patterns on the pulse oximetry measurements in systemic sclerosis patients.

Nailfold capillaroscopy is a simple method for determining microvascular damage in systemic sclerosis (SSc). The pulse oximeter is a noninvasive tool that is used to estimate a patient's arterial blood oxygen saturation. The aim of this study was to investigate the effect of capillaroscopic patterns on pulse oximetry measurements in SSc patients. The nailfolds from 2nd to 5th fingers in both hands were examined in all subjects by using capillaroscopy. Patients were categorized according to their capillaroscopy findings in 3 groups as having early, active or late patterns. Oxygen saturation (SpO2) measurements were performed from 2nd to 5th fingers in both hands with a finger probe. We studied 53 SSc patients (F/M: 48/5). According to capillaroscopy findings 18 patients were classified as having early pattern (34.0%), 19 active pattern (35.8%), and 15 late pattern (28.3%). Only 1 (1.9%) patient had normal capillaroscopy findings. SpO2 could not be measured in 47 (11.0%) fingers and in 20 (37.7%) SSc patients. There were 20 (37.7%) patients with a ≥4% difference between the minimum and maximum SpO2 measurements among fingers. There were no difference between the groups of SSc patients defined by capillaroscopy findings in terms of mean maximal SpO2 or mean minimal SpO2 measured from fingers (p NS, for all). Assessment of SpO2 values in patients with SSc is challenging. We did not detect any effect of capillaroscopic patterns on mean SpO2 values. On the other hand ≥4% difference between minimum and maximum SpO2 values measured from fingers of a patient may be considered as an indirect sign of microvascular damage. Assessment of the highest measured SpO2 values among the fingers of a patient may be more suitable in practice.

IgM memory B cells: a mouse/human paradox.

Humoral memory is maintained by two types of persistent cells, memory B cells and plasma cells, which have different phenotypes and functions. Long-lived plasma cells can survive for a lifespan within a complex niche in the bone marrow and provide continuous protective serum antibody levels. Memory B cells reside in secondary lymphoid organs, where they can be rapidly mobilized upon a new antigenic encounter. Surface IgG has long been taken as a surrogate marker for memory in the mouse. Recently, however, we have brought evidence for a long-lived IgM memory B cell population in the mouse, while we have also argued that, in humans, these same cells are not classical memory B cells but marginal zone (MZ) B cells which, as opposed to their mouse MZ counterpart, recirculate and carry a mutated B cell receptor. In this review, we will discuss these apparently paradoxical results.

Recurrent uveitis due to sildenafil usage in a patient with Behçet's disease.

Behçet's disease (BD) may cause uveitis and retinal vasculitis in nearly half of the patients. Uveitis is one of the most serious complications that can lead to blindness. Sildenafil (Viagra(R)) and the other phosphodiesterase type 5 (PDE5) inhibitors are the first-line options for the treatment of erectile dysfunction, but transient visual symptoms and serious ocular side effects have been reported in PDE5 inhibitor users. Herein, we report a case with BD who applied to our outpatient unit with recurrent uveitis after sildenafil therapy.

Tocilizumab for giant cell arteritis: an amazing result.

Giant cell arteritis (GCA), previously Horton's disease, is a systemic vasculitis affecting the middle-sized or large arteries in patients older than 50 years of age. The mainstay of the treatment of GCA is glucocorticoid therapy. Herein, we present a case with giant cell arteritis resistant to oral and intravenous steroid, intravenous cyclophosphamide and mycophenolate mofetil, but successfully treated with tocilizumab.

Triple DMARD combination for rheumatoid arthritis resistant to methotrexate and steroid combination: a single-center experience.

The mainstay of RA treatment is the disease-modifying antirheumatic drugs, and triple DMARD combination is now known to be better than monotherapies. Our aim in this trial was to report our clinical experience with triple DMARD therapy for resistant rheumatoid arthritis. Data of 140 patients with RA resistant to methotrexate and steroid combination were evaluated retrospectively. One hundred and nineteen (85 %) were female, and the median age at diagnosis was 56 (29-82) years. The median time between the diagnosis and beginning of triple therapy was 45.5 (6-564) months. Fifty-two (37.1 %) patients (group 1) on triple therapy protocol achieved remission, but the others (88; 62.9 %) (group 2) did not. The mean DAS28 scores for the study group before triple DMARD therapy and after 12 months under triple DMARD therapy were 4.93 and 3.24, respectively. The DAS28 scores after 12 months for groups 1 and 2 were 2.57 and 3.64. The median follow-up period for patients in group 1 was 60 months (23-118), and the mean DAS28 score at the time of the analysis for group 1 was 2.36. Triple DMARD combination may save one-third of the MTX-resistant RA patients from the serious side effects and the cost of anti-TNF.

Grape seed as a functional food ingredient in bread-making.

The objective of this study was to determine the effects of grape seed (GS) on the rheological and bread-making properties, antioxidant activity and phenolic composition of bread. Wheat flour was replaced with GS at levels of 2.5%, 5.0% and 7.5%. GS increased the dough development time at a level of 5.0% but did not change it at levels of 2.5% and 7.5%. The dough stability value increased from 6.4 to 12.3 min with the increase of GS content from 0% to 7.5%. Mixing tolerance index decreased from 41.1 to 6.4 Brabender Units Equivalent. Extensibility of dough containing GS was higher than that of the control dough. The antioxidant activities of the bread increased significantly with the increased GS substitution. Gallic acid and catechin content increased in the bread containing GS. It was concluded that GS could be added to the formulae to improve functionality of the bread.

Pulmonary hypertension in systemic lupus erythematosus: pulmonary thromboembolism is the leading cause.

BACKGROUND: Pulmonary hypertension (PH) is a life-threatening complication of systemic lupus erythematosus (SLE). Pulmonary hypertension in SLE has a variety of causes. Diagnosing early and defining the cause of PH accurately can provide better clinical outcome in SLE. We investigated the causes and characteristics of PH in patients with SLE. METHODS: One hundred twenty-one patients with SLE who had a visit in a 6-month period were assessed retrospectively. Patients who ever had a systolic pulmonary arterial pressure of 40 mm Hg or greater by Doppler echocardiography were considered to have PH. RESULTS: Among 122 patients, 65 had echocardiography for some reason, and 10 (8.2%) were diagnosed as having PH by echocardiographic examination. This number reduced to 9 (7.4%) when we excluded the patient with normal pulmonary artery pressure at right heart catheterization. Causes of PH were as follows: thromboembolic events in 4 patients (44.4%) (2 of them had chronic thromboembolic PH), left-sided heart disease in 2 patients (22.2%), pulmonary arterial hypertension in 1 patient (11.1%), high cardiac output state in 1 patient (11.1%), and transient elevation of systolic pulmonary artery pressure in 1 patient (11.1%) who had a history of venous thromboembolism. Venous thromboembolic disease was significantly higher in patients with SLE with PH in comparison to patients with SLE without PH (7 patients [6.3%] vs 5 patients [50.0%]; P = 0.001). All patients improved clinically during their short-term follow-up. CONCLUSIONS: Patients with SLE are at increased risk for PH. This study highlights the complexity of the differential diagnosis of PH in patients with SLE once again and emphasizes the importance of pulmonary thromboembolism as a cause of PH. One should investigate patients with SLE with unexplained symptoms and/or signs related to PH for possible treatable causes.

Vascular Involvement in Behcet's Disease: An Evaluation of 147 Cases and Literature Review.

Objectives: Behcet's disease (BD) is characterized by systemic vasculitis with inflammation that can affect various body organs. In BD, vasculitis primarily manifests with venous involvement, distinguishing it from other forms of systemic vasculitis. Methods: We retrospectively analyzed the demographic and clinical characteristics of 147 patients diagnosed with vascular BD in our center. Results: Vascular BD cases accounted for 25.0% (147 out of 589) of all BD patients. A statistically significant correlation was found between gender and vascular involvement that was seen predominantly in males (76.9%). In 71 patients, a vascular event developed during follow-up for BD, while in 76 patients the disease was diagnosed after the occurrence of a vascular event (51.7%). The most common vascular event was deep vein thrombosis in the lower extremities (69.4%). Arterial involvement was primarily observed in the pulmonary arteries (12.9%). Patients with lower extremity deep vein thrombosis tended to be younger, while those with pulmonary artery involvement were typically older. Overall, veins were affected 4.5 times more frequently than arteries. Conclusion: The prevalent type of venous involvement was deep vein thrombosis in the lower extremities. Thrombotic events in BD cannot be solely attributed to abnormalities in thrombotic factors. The treatment of thrombotic events in BD remains contentious, with anticoagulant efficacy being debated and immunosuppressive therapy representing the primary treatment approach. Behcet's disease should be considered when a young male patient presents with an arterial or venous vascular event, especially if it is recurrent.

Elevated Kynurenine Levels in Patients with Primary Sjögren's Syndrome.

OBJECTIVE: We aimed to investigate the plasma levels of tryptophan (Trp) and its metabolites in patients with primary Sjögren's syndrome (pSS). METHODS: The study included 34 pSS patients and 42 healthy individuals, and serum Trp and kynurenine (Kyn) concentrations were measured by liquid chromatography with tandem mass spectrometry. Trp degradation was predicted using the ratio of Kyn and Trp concentrations (Kyn/Trp). RESULTS: In our study, the mean serum Trp concentration was found to be considerably lower in the pSS group than in the control group (P = .001). The levels of Kyn (P = .019) and the Kyn/Trp ratio (P < .001) were significantly higher in the pSS group than in the control group. The Kyn/Trp ratio was negatively correlated with C-reactive protein (r = -0.369, P = .032). CONCLUSION: We found that Kyn pathway metabolism was altered in patients with pSS. This suggests that Trp metabolism may be closely linked to the disease pathogenesis of pSS.

14-3-3 η ETA protein as a potential marker of joint damage in gout.

INTRODUCTION: The aim of the study is to investigate serum levels of 14-3-3 η (ETA) protein in patients with gout and possible relations with joint damage. METHOD: This cross-sectional study included 43 gout patients and 30 control patients. RESULTS: Serum 14-3-3 η protein levels were significantly higher in gout patients (median [IQR], 3.1 [2.0] vs 2.2 [1.0], p = 0.007). In subgroup analyses of gout patients, serum 14-3-3 η protein levels did not differ between patients with and without a flare, tophaceous disease, elevated CRP and serum uric acid levels and a history of chronic kidney disease; however, were significantly higher in the patients with erosions (Median [IQR], 4.1 [2.7] vs 2.7 [1.5], p = 0.002). According to ROC curve, serum 14-3-3 η protein had 86.0% sensitivity and 30% specifity at a cut-off point of 1.7 ng/mL and had 74.7% sensitivity and 43.3% specifity at a cut-off point of 2.0 ng/mL. CONCLUSION: Our results demonstrated elevated levels of 14-3-3 η protein in gout patients which is more prominent in patients with erosive changes, implying role of 14-3-3 η protein in inflammatory and structural damage related pathways and suggesting a potential as a marker for disease severity.