Negative ANA-IIF in SLE patients: what is beyond?

The antinuclear antibody (ANA) test has high sensitivity in diagnosing and classifying systemic lupus erythematosus (SLE). OBJECTIVES: To describe the immunological pattern of SLE patients through investigating specific antinuclear autoantibodies by enzyme dot immunoassay and studying their frequency in both positive and negative ANA indirect immunofluorescence assay (IIF) cases. METHODS: In a cross-sectional study, blood samples from 393 newly diagnosed SLE patients were analyzed using (IIF) on HEp-2 cells and ANA dot immunoassay by automated enzyme immunoassay (EIA) to detect 19 antibodies. RESULTS: Ninety-one percent of the patients are females; their mean age was 37 ± 12.28. Antinuclear antibody (ANA) was detected by IIF in 82.4% of cases, with 181 (46.1%) speckled and 167 (42.4%) homogeneous ANA patterns. The majority of patients (96%) demonstrated autoantibodies via EIA. Among the ANA-IIF-negative patients, 97.2% demonstrated autoantibodies. There was a significant difference in the frequency of certain autoantibodies between SLE patients with negative and positive ANA-IIF (1.44 0.73, 3.12 2.09, p = 0.00) respectively. CONCLUSION: The results of analyzing 19 autoantibodies with the ANA staining pattern increased the significance of analyzing the immune profile even if IIF is negative when clinical symptoms strongly suggest SLE diagnosis. Certain autoantibodies may evade staining by the IFA approach while they are present in the patient's serum, and they may not be detected by the ANA EIA profile if it does not contain that antigenic substrate. Key Points • Indirect immunofluorescence on Hep-2 is the conventional method for ANA detection and is regarded as the "gold standard" for testing in clinical practice for SLE. • In our study, ANA profile dot enzyme immunoassay (EIA)-based test was performed to evaluate 19 autoantibodies in SLE patients either positive or negative for ANA-IIF. • The presence of anti-dsDNA with ANA-IIF-negative serum in 32.4% of SLE patients provides evidence that not all anti-dsDNA antibodies are identified on standard HEp-2 substrates. • certain autoantibodies can evade staining by the ANA-IIF method despite being present in the SLE patient's blood; this supports the ANA profile enzyme dot immunoassay as a more sensitive test.

Exists a role for serum irisin in Egyptian Behcet's patients with subclinical atherosclerosis?

OBJECTIVES: To examine the serum irisin level in a group of Behcet's disease patients, its association with illness parameters, and its utility in diagnosing subclinical atherosclerosis. METHODS: This randomized case-control study included 50 patients and 50 age- and sex-matched controls. Carotid Doppler ultrasound for the measurement of the carotid artery intima-media thickness (CIMT) and ankle-brachial pressure index (ABPI) were performed. A clinical evaluation, lipogram, and serum irisin were also performed. RESULTS: Between the patients and the control group, there was a significant difference in CIMT, S. irisin level, and ankle-brachial pressure index; however, gender and BMI did not significantly affect CIMT, ABPI, or S. irisin level. CIMT demonstrated a substantial negative correlation with both S. irisin and ABPI (r = - 0.62, P 0.0001). With a sensitivity of up to 94.30% and a specificity of 93.30%, the ROC analysis revealed that a decrease in S. irisin level in Behcet's patients was indicative of subclinical atherosclerosis. The drop in the ABPI level demonstrated a sensitivity of up to 94.30% and a specificity of 100%. CONCLUSION: Subclinical atherosclerosis is prevalent among Egyptian Behcet's patients, and S. irisin can be employed as a biomarker for diagnosing subclinical atherosclerosis in Behcet's illness. Key Points • Serum irisin has been studied in numerous autoimmune disorders as a marker for subclinical atherosclerosis, although its importance in Behcet's disease remains unclear (BD). • We examined the change in serum irisin levels in Behcet's disease patients and healthy controls. In addition, its association with carotid artery intima-media thickness (CIMT) and ankle-brachial pressure index was investigated (ABPI). • Changes in serum irisin levels are significant in BD, and a decrease in irisin level indicates subclinical atherosclerosis.

Study the Relationship of MDCT Staging in Disease Extent with the Systemic Sclerosis Disease Parameters.

BACKGROUND AND OBJECTIVES: The highest incidence of death in systemic sclerosis due to pulmonary disease raises the need for early detection and treatment. The study aim is the assessment of interstitial pulmonary disease by Multi Detector High Resolution CT (MDCT) and finds its relationship with the other disease parameters and the Pulmonary Function tests (PFT). PATIENTS AND METHODS: A prospective cross-sectional study was performed in Assiut University Hospitals from May 2018 to January 2020 and included 62 consecutive SSc female patients. Demographic, clinical, Laboratory, PFT and MDCT assessment were conducted for all participants. RESULTS: The coarseness of fibrosis was 8.32 (range 0.0-17), the average proportion of ground-glass opacification was 28.3% (range, 0.0%-75%). Honey-comb pattern was seen in (52.5%). Mean Extent of disease was 46.25±3.7 (range 5-81). Restrictive deficit found in 42 patients. Significant relation was found between the extent of disease and the percentage predicted FVC (r=0.373, p 0.018) and FEV1/FVC (r=0.593, p 0.000) and coarseness of fibrosis and proportion of ground glass opacification correlated inversely with VC (r=-0.385, p=0.014, r=-0.376, p=0.017 respectively), Rayanud's phenomena, modified Rodnan Skin Score and Medsger's general are positively correlated with MDCT disease extent. CONCLUSION: Scoring of systemic sclerosis (SSc) related interstitial lung disease (SSc-ILD) could be applicable as one of the important tools for disease assessment.

Study the Relationship of MDCT Staging in Disease Extent with the Systemic Sclerosis Disease Parameters.

BACKGROUND AND OBJECTIVES: The highest incidence of death in systemic sclerosis due to pulmonary disease raises the need for early detection and treatment. The study aim is the assessment of interstitial pulmonary disease by Multi Detector High Resolution CT (MDCT) and finds its relationship with the other disease parameters and the Pulmonary Function tests (PFT). PATIENTS AND METHODS: A prospective cross-sectional study was performed in Assiut University Hospitals from May 2018 to January 2020 and included 62 consecutive SSc female patients. Demographic, clinical, Laboratory, PFT and MDCT assessment were conducted for all participants. RESULTS: The coarseness of fibrosis was 8.32 (range 0.0-17), the average proportion of ground-glass opacification was 28.3% (range, 0.0%-75%). Honey-comb pattern was seen in (52.5%). Mean Extent of disease was 46.25±3.7 (range 5-81). Restrictive deficit found in 42 patients. Significant relation was found between the extent of disease and the percentage predicted FVC (r=0.373, p 0.018) and FEV1/FVC (r=0.593, p 0.000) and coarseness of fibrosis and proportion of ground glass opacification correlated inversely with VC (r=-0.385, p=0.014, r=-0.376, p=0.017 respectively), Rayanud's phenomena, modified Rodnan Skin Score and Medsger's general are positively correlated with MDCT disease extent. CONCLUSION: Scoring of systemic sclerosis (SSc) related interstitial lung disease (SSc-ILD) could be applicable as one of the important tools for disease assessment.

Peripheral cells from patients with systemic sclerosis disease co-expressing M1 and M2 monocyte/macrophage surface markers: Relation to the degree of skin involvement.

The monocyte/macrophage lineage cells were found involved in the pathogenesis of systemic sclerosis (SSc) disease. The naïve macrophages are activated either to M1 cells with proinflammatory roles or to M2 cells that function to resolve inflammation with tissue repair. Recently, cells with dual phenotypes were detected in SSc disease. So, we aimed in this study to demonstrate different monocyte/macrophage phenotypes in peripheral cells from a group of Egyptian SSc patients, correlating percentages of these cells with the clinical findings in patients. The study participants comprised 41 patients with diffuse cutaneous SSc disease and 25 healthy individuals as controls. Clinical, radiological, and laboratory tests were conducted for SSc patients. Different phenotypes of the monocyte/macrophage subsets were identified in peripheral blood of patients and controls by flow cytometry for characteristic M1 (CD80, CD86, and TLR4) and M2 (CD204, CD163 and CD206) markers. SSc patients showed higher percentages of peripheral cells of the M1, M2, and mixed M1/M2 phenotypes within the monocyte/macrophage lineage compared to controls. Different cell phenotypes were associated significantly with the disease duration, modified Rodnan's score, the Medsger skin score, and the Medsger lung in SSc patients. Some cells with the M1/M2 phenotypes were higher in SSc patients with pitting scars, arthritis, and myalgia.

Study of MRI brain findings and carotid US features in systemic sclerosis patients, relationship with disease parameters.

BACKGROUND/OBJECTIVES: Systemic sclerosis (SSc) is an autoimmune disease associated with immune abnormalities and widespread vascular lesions, including increased intimal and medial thickness. These changes may be reflected in early atherosclerosis and cardiovascular risks. We aimed in this study to examine the carotid artery intima-media thickness and MRI brain findings in SSc patients and compared them to a group of normal controls. A relationship between these parameters and clinical measures in SSc was also sought. METHODS: Seventy-two SSc patients with no central nervous system (CNS) symptoms and 42 healthy controls were included. Clinical and laboratory measures, Medsger's severity scale, and Doppler ultrasound common carotid artery intima-media thickness (CCA-IMT) were measured. Brain fluid-attenuated inversion recovery (FLAIR)-MRI and diffusion-weighted MRI (DWI) were also done. RESULTS: SSc patients had more CCA-IMT, higher CRP, and more brain MRI hyperintense lesions than controls (P < 0.05). Significant positive correlations existed between CCA-IMT and Medsger vascular (r = 0.7, P = 0.02). The FLAIR-MRI showed multiple hyperintense lesions in 24 patients (33%), ranging 0-36 lesions. SSc patients with more lesions (positive MRI) had longer disease duration (P = 0.001) and left and right carotid artery atheromata (P = 0.001, and 0.013, respectively) than SSc patients with negative MRIs; Medsger vascular score did not separate the SSc groups (P = 0.08). CONCLUSIONS: In systemic sclerosis patients without central nervous system symptoms, MRI lesion numbers correlated with CCA-IMT. MRI abnormalities were found more frequently if CRP was elevated, if the Medsger SSc Severity Scale was increased, or if there was thickened carotid IMT.

A Longitudinal Study of the 28 Joints of Disease Activity Score by Ultrasonographical Examination in Rheumatoid Arthritis Patients.

BACKGROUND: The damaging effect of rheumatoid arthritis (RA) on cartilage, bone, ligaments, and tendons has raised the importance of the disease activity and severity assessment to enable therapeutic decisions and to evaluate disease outcome. AIM: The aim is to compare the clinical examination of the Disease Activity Score (DAS)-28 with the musculoskeletal ultrasonography (US) examination in RA patients. Moreover, finding if we can use ultrasonographical results as a tool for predicting subsequent radiological damage. PATIENTS AND METHODS: It is a longitudinal study included 60 adult RA patients. Patients were under assessment at baseline, 6 months, and 12 months from the recruitment time. Twenty-eight joints of DAS were assessed for tenderness and swelling. US gray scale (GS) and US power Doppler (PD) score also was done at each visit. RESULTS: DAS-28, with its parameters, is positively and highly significantly correlated to synovitis severity both by US GS and US-PD score along the study follow-up visits. There was highly significant difference between the number of 28 swollen and tender joints by clinical examination with both US GS and US-PD. Linear regression analysis to predict the number of swollen and tender joints after 12 months showed significance between US PD with swollen and tender joints' numbers. The correlation was positive and significant between Larsen score at 12 months with GS US and PD US assessment, but linear regression analysis was only significant for Larsen score with only GS US. CONCLUSION: GS US and PD is a sensitive and reliable noninvasive method complementary to standard clinical assessment and could be a tool for predicting subsequent joints' damage.

Study of the osteoprotegerin/receptor activator of nuclear factor-kB ligand system association with inflammation and atherosclerosis in systemic sclerosis.

OBJECTIVE: we aimed to study systemic sclerosis patients in order to assess osteoprotegerin/Receptor activator of nuclear factor-kB ligand (OPG/RANKL) system and find the relation of these biomarkers with the clinical features of the disease, the carotid intima thickness, markers of inflammation, lipid profile, and other laboratory characteristics. METHODS: both the level of (RANKL), (OPG) in sera of participants, in 30 (SSc) patients and the atherosclerotic changes affecting the common carotid artery were measured and, were compared to 30 healthy controls matched for age and sex. All participants were assessed clinically and subjected to the Revised Medsger SSc severity scale and underwent carotid Doppler ultrasound examination. RESULTS: OPG, RANKL, and RANKL/OPG were 1.9 ± 0.4 ng/ml, 24.3 ± 17.25 ng/ml, and 13.5 ±9.8 versus 0.77 ± 0.25 ng/ml, 7.13 ± 3.02 ng/ml, and 9.6 ± 3.1 in the SSc patients and the controls with significance (P = 0.001, P = 0.001, P = 0.045) respectively. The OPG- RANKL axis in the SSc patients correlated significantly with carotid intima thickness, arthritis, arthralgia, inflammatory markers, Medsger joint, Medsger vascular, Medsger skin, and dyslipidemia. CONCLUSION: In cardiovascular risks, OPG serum level might increase as a preventive compensatory mechanism to neutralize the RANKL level increment. The determination of the OPG-RANKL system is a diagnostic indicator for the intensity of vascular calcification and atherosclerosis in SSc patients.

Is It the Age at Disease Onset or the Disease Radiological Severity That Affects Cervical Spine Involvement in Patients With Rheumatoid Arthritis?

BACKGROUND: Cervical spine involvement in patients with rheumatoid arthritis (RA) can cause pain and disability, with a variety of neurologic signs and symptoms. OBJECTIVES: To investigate the relationship between structural cervical spine involvement in patients with RA with the age at disease onset and the degree of radiologic severity of RA measured by Larsen scoring. PATIENTS AND METHODS: This cross-sectional study included 50 adult patients with RA. Patients who complained or not complained from symptoms of cervical spine involvement in RA were included; we did X-ray of the cervical spine, hands, and feet; Larsen scoring method; disease activity score (DAS28); and Neck Disability Index. RESULTS: The results revealed that patients with cervical involvement tend to be younger at their disease onset than those with no cervical involvement, as detected by cervical X-ray. The relation was significant P < .05 regarding all cervical involvements except for basilar invagination. Disease radiological severity (measured by Larsen score) significantly increases the risk for subaxial subluxation, P = .040. All other cervical complications of RA tend to have nonsignificant relation with disease severity. Using univariate binary regression analysis for risk factors for cervical involvement showed that the only probable risk factor for cervical involvement (detected by X-ray) in patients with RA is age at disease onset. CONCLUSIONS: The early age at disease onset tends to affect cervical spine involvement in patients with RA more than the disease radiological severity.

High-resolution manometry compared with the University of California, Los Angeles Scleroderma Clinical Trials Consortium GIT 2.0 in Systemic Sclerosis.

OBJECTIVES: To study esophageal high resolution manometry (HRM) in systemic sclerosis (SSc) patients and the correlation of findings to The University of California, Los Angeles Scleroderma Clinical Trials Consortium gastrointestinal tract 2.0 (UCLA SCTC_GIT 2.0). METHODS: Forty SSc patients were administered to the UCLA SCTC GIT 2.0. Patients underwent HRM study (Solar GI MMS). HRM data were compared with 15 healthy volunteers. RESULTS: Forty patients with mean age 46 ± 7 years and disease duration 9.3 ± 7 years reported upper (85.7%), lower GI symptoms (75%), while 5% reported no symptoms. Mean ± SD scores of UCLA SCTC_GIT 2.0 items were as follows: reflux 1.2 ± 0.8, distention 1.6 ± 1.2, fecal soiling 0.3 ± 0.9, diarrhea 0.8 ± 1, social 1 ± 1, emotional 1 ± 1.1, constipation 0.5 ± 0.9, and total GIT score 0.9 ± 0.6. Lower esophageal sphincter (LES) pressure and distal esophageal amplitude were significantly lower in SSc patients than controls. Main manometric findings were decreased LES resting pressure (40%) and aperistalsis (40%). Regression analyses showed distal esophageal amplitude and LES resting pressure negatively correlated with reflux score (r = -0.64; p = 0.001 and r = -0.46; p = 0.019, respectively), and total GIT score (r = -0.54; p = 0.007 and r = -0.42; p = 0.03, respectively). LES resting pressure had negative correlations with diarrhea score (r = -0.062; p = 0.002). CONCLUSIONS: Decreased distal esophageal amplitude encountered as hypoperistalsis or even aperistalsis was associated with increased reflux and GIT scores (negatively correlated) UCLA SCTC_GIT 2.0 questionnaires. The GIT2.0 is easy to use and can serve as an indicator that further testing of the GI tract, including the esophagus, is indicated.