Population distribution and clinical characteristics in rheumatoid arthritis patients with cervical spine instability / 北京大学学报(医学版)

OBJECTIVE@#To investigate the population distribution of cervical spine instability in rheumatoid arthritis (RA) patients, and to analyze the clinical characteristics in RA patients with cervical spine instability.@*METHODS@#A total of 439 RA patients who had completed cervical spine X-ray examination from Department of Rheumatology and Immunology of Peking University Shenzhen Hospital and Peking University Third Hospital from August 2015 to March 2019 were enrolled. The clinical data, laboratory data and cervical radiographic data were collected and analyzed by t-test, rank sum test and Chi-square test to clarify the clinical characteristics in the RA patients with cervical spine instability.@*RESULTS@#Of the 439 RA patients, 80.9% (355/439) were female, with an average age of (52.9±13.9) years, a median duration of the disease was 60 months, the shortest history was 2 weeks, and the longest history was up to 46 years. 29.6% (130/439) of the RA patients showed cervical spine instability. Among them, 20 RA patients were complicated with two different types of cervical instability, the atlantoaxial subluxation (AAS) accounted for 24.6% (108/439), the vertical subluxation (VS) accounted for 7.3% (32/439) and the subluxial subluxations (SAS) accounted for 2.3% (10/439). The patients with cervical spine instability had a longer duration of disease [120 (36, 240) months vs. 48 (12, 120) months], a higher proportion of peripheral joint deformity (56.9% vs. 29.9%), and a higher visual analog scale (VAS) measuring general health score (4.89±2.49 vs. 3.93±2.38), a lower hemoglobin [(111.31±19.44) g/L vs. (115.56±16.60) g/L] and a higher positive rate of anti-cyclic citrullina-ted peptide (CCP) antibody (90.8% vs. 76.6%). There were no significant differences in gender, age, number of swollen joints, number of tenderness joints, erythrocyte sedimentation rate, rheumatoid factor level, 28-joint disease activity score, positive rate of anti keratin antibody, duration of glucocorticoid use and duration of disease modifying anti-rheumatic drugs use between the two groups.@*CONCLUSION@#In the study, 29.6% of the RA patients showed cervical spine instability. RA patients with cervical spine instability had a long-term disease, a higher proportion of peripheral joint deformity, a higher VAS measuring general health score, a lower hemoglobin and a higher positive rate of anti-CCP antibody.

Change of serum B-cell activating factor level in patients with positive antiphospholipid antibodies and previous adverse pregnancy outcomes and its significance / 中华医学杂志(英文版)

BACKGROUND@#B-cell activating factor (BAFF) is vital for B cell survival. Serum BAFF levels are elevated in thrombotic antiphospholipid syndrome, but little is known about levels in patients with positive antiphospholipid antibodies (aPLs) and previous adverse pregnancy outcomes (APOs). We aimed to analyze serum BAFF concentrations of these patients in early pregnancy along with different pregnancy outcomes.@*METHODS@#Thirty-six pregnant patients positive for aPLs and previous APOs (patient group), 25 healthy pregnant females (HP group) and 35 healthy non-pregnant females (HNP group) from the Peking University Third Hospital, between October 2018 and March 2019, were enrolled in this study. Serum of HNP and serum of patients as well as HP in the first gestational trimester were collected. Enzyme-linked immunosorbent assay kits were used to measure serum BAFF and interferon-alpha (IFN-α) concentrations. Cytometric bead array analysis was used to measure serum concentrations of cytokines. The patient group was further divided into APOs and non-APOs (NAPOs) group, fetal loss and live birth group according to pregnancy outcomes. The Mann-Whitney U-test was used to assess significance between and within groups. Spearman rank-order was used to evaluate correlation coefficients between BAFF and related cytokines.@*RESULTS@#The serum BAFF level in HP group was significantly lower than HNP group (245.24 [218.80, 265.90] vs. 326.94 [267.31, 414.80] pg/mL, Z = -3.966, P < 0.001). The BAFF level was obviously elevated in patient group compared to that in HP group (307.77 [219.86, 415.65] vs. 245.24 [218.80, 265.90] pg/mL, Z = -2.464, P = 0.013). BAFF levels in APOs group tended to be higher than that in NAPOs group (416.52 [307.07, 511.12] vs. 259.37 [203.59, 375.81] pg/mL, Z = -2.718, P = 0.006). Compared to HP group, concentrations of IFN-α, interleukin (IL-6) and tumor necrosis factor were higher in patient group (33.37 [18.85, 48.12] vs. 13.10 [6.85, 25.47] pg/mL, Z = -2.023, P = 0.043; 39.16 [4.41, 195.87] vs. 3.37 [2.92, 3.90] pg/mL, Z = -3.650, P < 0.001; 8.23 [2.27, 64.46] vs. 1.53 [1.25, 2.31] pg/mL, Z = -3.604, P < 0.001, respectively). Serum BAFF levels had a positive correlation with the concentrations of both IL-6 and IL-10 (IL-6: r = 0.525, P = 0.002; IL-10: r = 0.438, P = 0.012).@*CONCLUSIONS@#Serum BAFF levels are increased in patients with positive aPLs and previous APOs as compared to healthy pregnant females and tend to be higher in individuals with current APOs. The BAFF levels have a positive correlation with serum IL-6 and IL-10.

Progressive pseudorheumatoid dysplasia misdiagnosed as ankylosing spondylitis: a case report / 北京大学学报(医学版)

In this study, we reported a case of progressive pseudorheumatoid dysplasia in Peking University Third Hospital. A 56-year-old male patient presented with hip joint pain for more than 40 years and multiple joints pain with limitation of movements of these joints for 28 years. This patient suffered from joint pain and impaired range of motion of the hip, knee, elbow and shoulder gradually, associated with difficulty in walking and inability to take care of himself. He was diagnosed with "femoral head necrosis" or "ankylosing spondylitis" in local hospitals, but the treatment of nonsteroidal antiinflammatory drugs (NSAIDs) and sulfasalazine was not effective. Up to the age of 14, the patient displayed normal physical development, with the highest height was about 158 cm, according to the patient recall. However, his height was 153 cm at present. There was no history of similar illness in any family member. Physical examinations descried limitation of movement of almost all joints. Enlargement and flexion deformity of the proximal interphalangeal (PIP) joints of the hands resulted in the claw hand appearance. Limited abduction and internal and external rotation of the shoulder and hip could be find. He had normal laboratory findings for blood routine test, biochemical indexes and acute phase reactants such as C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR). Furthermore, HLA-B27 and autoimmune antibodies such as rheumatoid factor (RF), anti-cyclic citrullinated peptide (anti-CCP) antibody and antinuclear antibody (ANA) were all negative. X-ray of the hip showed loss of the joint space and irregularities of the femoral head, both femoral head were flattened, it could be see hyperplasia, osteophytes, bilateral femoral neck thicken, neck dry angle turned smaller. The radiological findings of the spinal vertebra indicated kyphosis deformity, narrowing of the intervertebral discs, vertebral syndesmophytes and flattening of the vertebra. However, there was no clues of bone marrow edema in the lumbar MRI. At last, genetic testing for the Wnt1-inducible signaling pathway protein 3 (WISP3) gene was done and indicated compound heterozygous mutations: 756C>G and c.866dupA. These two mutations were derived from the patient's mother and father (the patient's parents each had a heterozygous mutation). Two exons of the WISP3 gene had nucleotide changes leading to amino acid mutations. According to the patient's history, symptoms, physical examinations, radiological findings and genetic testing, the final definitive diagnosis was progressive pseudorheumatic dysplasia.

Diagnosis and treatment of antiphospholipid antibody-related recurrent spontaneous abortion and analysis of therapeutic drugs and pregnancy outcome in 75 patients with antiphospholipid syndrome / 北京大学学报(医学版)

Recurrent spontaneous abortion is one of the common complications in women of childbearing age during pregnancy. The immune factor accounts for a large proportion of many causes. Antiphospholipid antibody syndrome is the most common type of acquired thrombophilia disease. Autoimmune diseases that cause thrombosis and obstetric complications under the action of antibodies are also the most common type of immune-related recurrent abortion. At present, there is no unified opinion on the treatment of this disease, especially the treatment of immunoglobulins and other drugs like glucocorticoid. Here we reviewed the progress of diagnosis and treatment of antiphospholipid antibody-related recurrent abortions and retrospectively analyzed and summarized the drug regimens and pregnancy outcomes of this disease with pregnancy patients in our hospital. A total of 75 patients were included. According to their clinical manifestations and laboratory results, these patients were basically divided into two categories: classical antiphospholipid syndrome and non-classical antiphospholipid syndrome. The latter was further divided into serum-negative antiphospholipid syndrome and antiphospholipid antibody-related recurrent abortion patients based on their clinical manifestations and antiphospholipid antibody results. The patients were divided into four categories: aspirin + hydroxychloroquine, aspirin + low molecular weight heparin, aspirin + low molecular weight heparin + hydroxychloroquine, aspirin + hydroxychloroquine + low molecular weight heparin + low dose glucocorticoids. Among them, aspirin + hydroxychloroquine + low molecular weight heparin + low dose glucocorticoid treatment regimen was most commonly used. Most of the patients who received the above different treatment regimens achieved full-term infants, and a small number of patients had adverse pregnancy outcomes, such as premature delivery, placental abruption, eclampsia, and fetal malformation. And adverse pregnancy outcomes also occurred in this group. It might be related to the severity of the disease and the potential adverse effects of maternal fetal. However, further statistical analysis is needed for the risk factors affecting the pregnancy outcome of this part of patients.

Rs548234 polymorphism at PRDM1-ATG5 region susceptible to rheumatoid arthritis in Caucasians is not associated with rheumatoid arthritis in Chinese Han population / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>A previous study has shown that rs548234 polymorphism at PRDM1-ATG5 region is associated with rheumatoid arthritis (RA) in Caucasian populations. The aim of this study was to investigate the effect of rs548234 polymorphism at PRDM1-ATG5 region on susceptibility to RA in Chinese Han population.</p><p><b>METHODS</b>We genotyped 848 RA patients and 1431 matched healthy controls for rs548234 single-nucleotide polymorphism (SNP) with a predesigned TaqMan SNP genotyping assay. Association analyses were performed on the whole data set and on rheumatoid factors (RF) and anti-cyclic citrullinated peptides (anti-CCP) antibody. Finally, we carried out combined analysis of rs548234 association with RA based on the published data.</p><p><b>RESULTS</b>No significant difference in the genotype distribution between RA patients and healthy controls for rs548234 (C/T) polymorphism was found in Chinese Han population, neither in whole data set nor in stratified subsets, e.g. RF and anti-CCP status. Association analysis in different ethnic groups showed that rs548234 at PRDM1-ATG5 region was associated with RA in Caucasian ancestry but not in East Asian population.</p><p><b>CONCLUSIONS</b>Our results showed no involvement of rs548234 at PRDM1-ATG5 region in the susceptibility or clinical relevance of RA in Chinese Han population.</p>

Variation in STAT4 is associated with systemic lupus erythematosus in Chinese Northern Han population / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Recent studies have identified signal transducer and activator of transcription 4 (STAT4) as a susceptibility gene for systemic lupus erythematosus (SLE) in different populations. In order to examine whether the allele distribution of the single nucleotide polymorphism (SNP) in gene STAT4 rs7574865 in patients with SLE is different from those of healthy controls in Chinese Northern Han population, we investigated whether the variants of STAT4 rs7574865 were associated with any specific clinical features of SLE.</p><p><b>METHODS</b>We genotyped SNPs in STAT4 rs7574865 in 252 patients with SLE and 497 healthy controls. All subjects were from the Northern part of Chinese Han population. The genotypes in rs7574865 were determined by polymerase chain reaction (PCR) and consequence direct sequencing of PCR products in the DNA samples.</p><p><b>RESULTS</b>There was a significant difference in distribution of the SNPs in rs7574865 between the SLE patients and healthy controls. Compared with healthy controls, there was a significant correlation between TT genotypes in rs7574865 and the risk of SLE when GG genotype was used as a reference genotype after adjusting for gender and age. The frequency of T allele in the SLE patients was strongly significantly higher than that of healthy controls. Furthermore, there was a significant difference in the distribution of SNP in rs7574865 between male and female SLE patients, when compared with healthy controls. The frequency of T allele in rs7574865 in male patients was significantly higher than that of male healthy controls or female patients. There was no significant correlation between the frequencies of T allele in STAT4 rs7574865 and the clinical features of SLE.</p><p><b>CONCLUSIONS</b>The SNP rs7574865 in STAT4 is strongly associated with risk of SLE in the Chinese Northern Han population. The TT genotype and T allele in STAT4 rs7574869 are susceptibility factors for SLE, especially for male SLE patients.</p>

Juvenile psoriatic arthritis / 中国当代儿科杂志

A case of juvenile psoriatic arthritis in a 12 year-old boy was reported. The patient had a history of one and half a year of bilateral heel pain, followed by pain in the right knee and ankle and right hip joint. He developed psoriatic lesions affecting his nails and skin. He had increased erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) contents. Human leukocyte antigen (HLA) B27 was detected but serum rheumatoid factor was not in the patient. A skin biopsy revealed psoriasis and ultrasonography demonstrated synovitis in right knee and ankle. Juvenile psoriatic arthritis was diagnosed based on his physical, laboratory and skin biopsy findings. A treatment with nonsteroidal anti-inflammatory drugs and sulfasalazine produced no effect. Leflunomide in conjunction with anti-TNF biologic agents (Etanercept) was administered, followed by symptomatic improvement 2 weeks later.