Combined immunodeficiency (CVID and CD4 lymphopenia) is associated with a high risk of malignancy among adults with primary immune deficiency

Primary immunodeficiency disorders (PID) are a group of heterogeneous disorders characterized by recurrent infections, autoimmunity, increased lymphoproliferative disorders and other malignancies. PID is classified into cellular or humoral disorders or a combination of both. We evaluated the clinical differences among adult patients with three variants of PID: common variable immunodeficiency (CVID), idiopathic CD4 lymphopenia (ICL) and combined immunodeficiency (CID). We retrospectively compared demographics, immunological characteristics, clinical presentations and outcomes of CVID, CID and ICL patients followed from 2012 to 2018. In our cohort, we identified 44 adult patients diagnosed with CVID (22), CID (11) and ICL (11). Malignancy was associated with CID, as seven of 11 patients in this group were diagnosed with malignancy compared to CVID (three of 22) or ICL (two of 11) (P = 0·002 and 0·03, respectively). Malignancies were also linked to male gender [odds ratio (OR) = 5, 95% confidence interval (CI) = 1·12-22·18) P = 0·0342] and a low ratio of CD4/CD8 < 0·8 (OR = 5·1, 95% CI = 1·22-21·28, P = 0·025). Among CID and ICL, two of 11 patients died in each group, while no death was documented among CVID group (P = 0·04). Autoimmune manifestations did not differ between groups. Similarly, the rate of infections was similar between groups, although infectious agents vary. CID is associated with a high risk of malignancy compare to CVID or ICL. Among adults with PID, male gender, low CD4 and a CD4/CD8 ratio of < 0·8 may serve as risk factors of concomitant malignancy. Surveillance of lymphocyte subpopulations should be considered for all adults.

Alopecia areata in patients with systemic lupus erythematosus treated with belimumab: a plausible association.

Belimumab, an anti-B-lymphocyte stimulator monoclonal antibody, was recently approved for the treatment of systemic lupus erythematosus. Alopecia areata is characterized by an acute immune-mediated hair loss. Herein, we report on three adult systemic lupus erythematosus patients who developed alopecia areata in association with belimumab treatment. Alopecia areata was resolved in all three patients and belimumab was discontinued in two of them. Thus, in the current report, we explore the plausible link between alopecia areata and belimumab.

Chronic urticaria and osteoporosis: a longitudinal, community-based cohort study of 11 944 patients.

BACKGROUND: Chronic urticaria (CU) carries many risk factors for osteoporosis, but data on the relationships between CU and osteoporosis are lacking. OBJECTIVES: To evaluate the association between CU and osteoporosis in a large community-based study. METHODS: A nationwide observational longitudinal cohort study was conducted. CU was defined as four pairs of urticaria diagnoses; each pair was recorded within a period of 6 weeks and was registered by physicians in a primary-care setting. Patients with CU and their age- and sex- matched controls were followed for the incidence of osteoporosis and other laboratory data between 2002 and 2017. Data regarding systemic steroid exposure and other relevant risk factors for osteoporosis were obtained. Analyses of risk for osteoporosis were performed in Cox regression models adjusted for age, sex, exposure to systemic corticosteroids, obesity, smoking and hyper- and hypothyroid disease. RESULTS: The study included 11 944 patients with CU and 59 829 controls. During the study's observation period, 1035 (8·7%) patients with CU were diagnosed with osteoporosis, compared with 4046 (6·8%) controls. The adjusted multivariate analysis demonstrated that CU was significantly associated with a higher risk for osteoporosis (hazard ratio 1·23, 95% confidence interval 1·10-1·37, P < 0·001). CONCLUSIONS: CU may impose a risk for osteoporosis. Appropriate targeted screening should be considered.

Hydroxychloroquine desensitization, an effective method to overcome hypersensitivity-a multicenter experience.

Hydroxychloroquine (HCQ) is widely used to treat autoimmune/rheumatic diseases such as systemic lupus erythematosus (SLE). The immune modulation effects of HCQ have been highlighted as beneficial for maintaining remission of SLE as well as ameliorating skin, joint and other manifestations. Moreover, HCQ exposure for prolonged periods as well as during pregnancy is considered safe, therefore it is recommended for the vast majority of SLE patients. Although HCQ therapy requires follow-up by a specialist, its most common side effects are mild gastrointestinal disturbances, sensitivity to light and skin rashes. Of these side effects, hypersensitivity skin reactions have been suggested to play a role in reduced compliance to HCQ therapy. In the current study we present a two-stage HCQ desensitization protocol that was successfully implemented among 12 out of 13 patients. We exhibit that prolonged HCQ oral desensitization is an effective method for overcoming mild to moderate late hypersensitivity reactions and thoroughly address possible mechanisms of action.

Chronic urticaria and the metabolic syndrome: a cross-sectional community-based study of 11 261 patients.

BACKGROUND: Emerging evidence suggests that chronic urticaria (CU) is associated with chronic, low-grade, inflammatory process. OBJECTIVE: To evaluate the association between CU and metabolic syndrome and its components in a large community-based medical database. METHODS: A cross-sectional study of CU patients and matched controls was performed. CU was defined as eight urticaria diagnoses (with each two diagnoses registered within a period of 6 weeks) from 2002 to 2012. Data regarding the prevalence of metabolic syndrome, its components and possible complications were collected. RESULTS: The study included 11 261 patients with CU and 67 216 controls. In a univariate analysis, CU was significantly associated with higher body mass index (BMI) and a higher prevalence of obesity, diabetes, hyperlipidaemia, hypertension, metabolic syndrome, chronic renal failure and gout. Multivariate analysis demonstrated a significant association between CU and metabolic syndrome (OR = 1.12, 95% CI 1.1-1.2, P < 0.001) and its components - obesity (OR = 1.2, 95% CI 1.1-1.3, P < 0.001), diabetes (OR = 1.08, 95% CI 1.01-1.15, P = 0.001), hyperlipidaemia (OR = 1.2, 95% CI 1.1-1.2, P < 0.001) and hypertension (OR = 1.1, 95% CI 1.1-1.2, P < 0.001). CONCLUSIONS: CU patients may have one or more undiagnosed components of metabolic syndrome despite their young age. Thus, appropriate targeted screening is advised.

EULAR recommendations for women's health and the management of family planning, assisted reproduction, pregnancy and menopause in patients with systemic lupus erythematosus and/or antiphospholipid syndrome.

OBJECTIVES: Develop recommendations for women's health issues and family planning in systemic lupus erythematosus (SLE) and/or antiphospholipid syndrome (APS). METHODS: Systematic review of evidence followed by modified Delphi method to compile questions, elicit expert opinions and reach consensus. RESULTS: Family planning should be discussed as early as possible after diagnosis. Most women can have successful pregnancies and measures can be taken to reduce the risks of adverse maternal or fetal outcomes. Risk stratification includes disease activity, autoantibody profile, previous vascular and pregnancy morbidity, hypertension and the use of drugs (emphasis on benefits from hydroxychloroquine and antiplatelets/anticoagulants). Hormonal contraception and menopause replacement therapy can be used in patients with stable/inactive disease and low risk of thrombosis. Fertility preservation with gonadotropin-releasing hormone analogues should be considered prior to the use of alkylating agents. Assisted reproduction techniques can be safely used in patients with stable/inactive disease; patients with positive antiphospholipid antibodies/APS should receive anticoagulation and/or low-dose aspirin. Assessment of disease activity, renal function and serological markers is important for diagnosing disease flares and monitoring for obstetrical adverse outcomes. Fetal monitoring includes Doppler ultrasonography and fetal biometry, particularly in the third trimester, to screen for placental insufficiency and small for gestational age fetuses. Screening for gynaecological malignancies is similar to the general population, with increased vigilance for cervical premalignant lesions if exposed to immunosuppressive drugs. Human papillomavirus immunisation can be used in women with stable/inactive disease. CONCLUSIONS: Recommendations for women's health issues in SLE and/or APS were developed using an evidence-based approach followed by expert consensus.

Chondrodysplasia with multiple dislocations: comprehensive study of a series of 30 cases.

The group of chondrodysplasia with multiple dislocations includes several entities, characterized by short stature, dislocation of large joints, hand and/or vertebral anomalies. Other features, such as epiphyseal or metaphyseal changes, cleft palate, intellectual disability are also often part of the phenotype. In addition, several conditions with overlapping features are related to this group and broaden the spectrum. The majority of these disorders have been linked to pathogenic variants in genes encoding proteins implicated in the synthesis or sulfation of proteoglycans (PG). In a series of 30 patients with multiple dislocations, we have performed exome sequencing and subsequent targeted analysis of 15 genes, implicated in chondrodysplasia with multiple dislocations, and related conditions. We have identified causative pathogenic variants in 60% of patients (18/30); when a clinical diagnosis was suspected, this was molecularly confirmed in 53% of cases. Forty percent of patients remain without molecular etiology. Pathogenic variants in genes implicated in PG synthesis are of major importance in chondrodysplasia with multiple dislocations and related conditions. The combination of hand features, growth failure severity, radiological aspects of long bones and of vertebrae allowed discrimination among the different conditions. We propose key diagnostic clues to the clinician.

Focal demyelinative damage and neighboring white matter integrity: an optic neuritis study.

BACKGROUND: Neuronal loss following damage is often greater than expected from the severity of injury to the nerve itself. The visual pathways, which comprise a well-defined system, and optic neuritis (ON), which is usually a discrete event, make a fine model to study this phenomenon. OBJECTIVE: Understand the effect of focal optic nerve demyelination on neighboring white matter. METHODS: Diffusion tensor imaging and probabilistic tractography were used to identify and characterize the optic tracts and radiations of 17 ON and matched controls. Data were correlated with retinal nerve fiber layer (RNFL) thickness. RESULTS: Patients' optic tracts exhibited reduced axial diffusivity, which correlated with RNFL thickness values. Patients' optic radiations demonstrated intact axial diffusivity but reduced fractional anisotropy and elevated radial diffusivity, which could be explained by intra-bundle lesions. No correlations were found between diffusivity measurements in patients' optic tracts and radiations; or between RNFL thickness and optic radiations' diffusivity. CONCLUSIONS: Following ON, chronic axonal loss develops distally in the optic tracts, demonstrating Wallerian degeneration. Degeneration did not proceed to the optic radiations, opposing anterograde trans-neuronal changes. DTI in ON provides fine in-vivo human model for studying histological abnormalities in normal appearing white matter, localized in close proximity to damaged bundle.

Androgen Receptor CAG Repeat Length in Relation to Phenotype Among Females with Nonclassical 21-Hydroxylase Deficiency.

Nonclassical 21-hydroxylase deficiency (NC21OHD) manifests with various degrees of post natal virilization. The length of CAG repeats of the androgen receptor gene (AR) is inversely correlated to activity of the human androgen receptor (AR) and affects phenotype of several androgen-dependent disorders. The aim of the study was to investigate the associations between CAG repeat length and the phenotype of females with NC21OHD. CAG repeat length and AR inactivation were assessed in females with NC21OHD, and related to their clinical presentation. CAG repeat length and AR inactivation were assessed in 119 females with NC21OHD. Biallelic mean (BAM) of the CAG repeat length and the weighted BAM (WBAM) were related to various clinical parameters. Age at diagnosis and age of menarche positively correlated with BAM (r=0.22, p=0.02, and r=0.23, p=0.01, respectively). A shorter (<25) BAM was associated with younger age at diagnosis (14.8 vs. 21.4 years, p<0.01), at adrenarche (8.1 vs. 10.2 years, p<0.01) and gonadarche (9.9 vs. 11.2 years, p<0.01), and higher corrected height standard deviation score at diagnosis (0.77 vs. 0.15, p=0.01). Precocious pubarche and precocious puberty were more frequent in these with the shorter BAM. Results of WBAM were similar. The CAG repeat length of the AR gene contributes to the clinical diversity of the phenotype in females with NC21OHD.

Contamination history of lead and other trace metals reconstructed from an urban winter pond in the Eastern Mediterranean coast (Israel).

Pollution history of Pb and other trace metals was reconstructed for the first time for the Eastern Mediterranean, from a small urban winter pond (Dora, Netanya), located at the densely populated coastal plain of Israel. An integrated approach including geochemical, sedimentological, and historical analyses was employed to study sediments from the center of the pond. Profiles of metal concentrations (Pb, Zn, V, Ni, Cu, Cr, Co, Cd, and Hg) and Pb isotopic composition denote two main eras of pre- and post-19th century. The deeper sediment is characterized by low concentrations and relatively constant 206Pb/207Pb (around 1.20), similar to natural Pb sources, with slight indications of ancient anthropogenic activity. The upper sediment displays an upward increase in trace metal concentrations, with the highest enrichment factor for Pb (18.4). Lead fluxes and isotopic composition point to national/regional petrol-Pb emissions as the major contributor to Pb contamination, overwhelming other potential local and transboundary sources. Traffic-related metals are correlated with Pb, emphasizing the polluting inputs of traffic. The Hg profile, however, implies global pollution rather than local sources.

Ferritin in the antiphospholipid syndrome and its catastrophic variant (cAPS).

BACKGROUND: Ferritin is an iron storage protein considered also as an acute phase reactant with high levels in various inflammatory conditions. Recently, a plausible role for ferritin in the pathogenesis of immune-mediated and especially autoimmune diseases has been suggested. However, the link between ferritin and the antiphospholipid syndrome (APS) has been rarely explored. Therefore, in the current study we evaluated ferritin levels and their correlation to clinical and serological manifestations in patients with APS. We further analyzed ferritin levels among patients with the catastrophic variant of APS (cAPS). METHODS: Ferritin levels were determined in serum samples of 176 APS patients and 98 matched healthy controls according to age and sex (LIAISON, DiaSorin, Italy). APS samples were further analyzed for antiphospholipid (anti-cardiolipin, anti- beta-2-glycoprotein, lupus anticoagulant) and anti-infectious antibodies (CMV, EBV, rubella, toxoplasma, HBV) (LIAISON, DiaSorin, Italy). Clinical, serological and demographic manifestations were recorded. An additional analysis of ferritin levels among 14 patients with cAPS was performed. RESULTS: Hyperferritinemia was present in 9% vs. 0% of APS patients and controls, respectively (p < 0.001). Among patients with APS, ferritin levels correlated with venous thrombosis, cardiac, neurological, and hematological manifestations and the presence of anti-CMV-IgM antibodies. Hyperferritinemia was present in 71% of cAPS patients, and ferritin levels among this subgroup were significantly higher compared with APS-non-cAPS patients (816 ± 847 ng/ml vs. 120 ± 230 ng/ml, p < 0.001). CONCLUSIONS: Herein, we found that hyperferritinemia correlates with the presence of APS, its clinical manifestations and specifically with the catastrophic variant of this disease. Hyperferritinemia was also linked with anti-CMV antibodies among patients with APS. These associations allude to a pathogenic role of ferritin in the pathogenesis of APS, and the plausible role of ferritin as a marker of ensuing cAPS, although further studies are needed to elucidate these associations.

Seasonal Variations in Triple Oxygen Isotope Ratios of Precipitation in the Western and Central United States.

Triple oxygen isotope ratios Δ'17O offer new opportunities to improve reconstructions of past climate by quantifying evaporation, relative humidity, and diagenesis in geologic archives. However, the utility of Δ'17O in paleoclimate applications is hampered by a limited understanding of how precipitation Δ'7O values vary across time and space. To improve applications of Δ'17O, we present δ18O, d-excess, and Δ'17O data from 26 precipitation sites in the western and central United States and three streams from the Willamette River Basin in western Oregon. In this data set, we find that precipitation Δ'17O tracks evaporation but appears insensitive to many controls that govern variation in δ18O, including Rayleigh distillation, elevation, latitude, longitude, and local precipitation amount. Seasonality has a large effect on Δ'17O variation in the data set and we observe higher seasonally amount-weighted average precipitation Δ'17O values in the winter (40 ± 15 per meg [± standard deviation]) than in the summer (18 ± 18 per meg). This seasonal precipitation Δ'17O variability likely arises from a combination of sub-cloud evaporation, atmospheric mixing, moisture recycling, sublimation, and/or relative humidity, but the data set is not well suited to quantitatively assess isotopic variability associated with each of these processes. The seasonal Δ'17O pattern, which is absent in d-excess and opposite in sign from δ18O, appears in other data sets globally; it showcases the influence of seasonality on Δ'17O values of precipitation and highlights the need for further systematic studies to understand variation in Δ'17O values of precipitation.

Breast cancer and other neoplasms in women with neurofibromatosis type 1: a retrospective review of cases in the Detroit metropolitan area.

Neurofibromatosis type 1 (NF1) is one of the most common cancer predisposing syndromes with an incidence of 1 in 3,500 worldwide. Certain neoplasms or malignancies are over-represented in individuals with NF1; however, an increased risk of breast cancer has not been widely recognized or accepted. We identified 76 women with NF1 seen in the Henry Ford Health System (HFHS) from 1990 to 2009, and linked them to the Surveillance Epidemiology and End Results (SEER) registry covering the metropolitan Detroit area. Fifty-one women (67%) were under age 50 years at the time of data analysis. Six women developed invasive breast cancer before age 50, and three developed invasive breast cancer after age 50. Using standardized incidence ratios (SIRs) calculated based on the SEER age-adjusted invasive breast cancer incidence rates, our findings demonstrated a statistically significant increase of breast cancer incidence occurring in NF1 women (SIR = 5.2; 95% CI 2.4-9.8), and this relative increase was especially evident among those with breast cancer onset under age 50 (SIR = 8.8; 95% CI 3.2-19.2). These data are consistent with other reports suggesting an increase in breast cancer risk among females with NF1, which indicate that breast cancer screening guidelines should be evaluated for this potentially high-risk group.

Silicone and scleroderma revisited.

Silicone, a synthetic polymer considered to be a biologically inert substance, is used in a multitude of medical products, the most publicly recognized of which are breast implants. Silicone breast implants have been in use since the early 1960s for cosmetic and reconstructive purposes, and reports of autoimmune disease-like syndromes began appearing in the medical literature soon thereafter. Over the previous year, silicone implants have been suggested as playing a role in a new syndrome that encompasses a wide array of immune-related manifestations, termed ASIA ('Autoimmune Syndrome Induced by Adjuvant'). Scleroderma, a relatively rare connective tissue disease with skin manifestations and systemic effects, has also been described in association with silicone implantation and rupture. However, epidemiological studies and meta-analyses have failed to corroborate the clinical impression of silicone-induced scleroderma. The following review describes the mechanisms by which silicone may mediate autoimmunity in general, as well as the evidence for causal associations with more specific autoimmune syndromes in general, and scleroderma in particular.

Autoimmunity following hepatitis B vaccine as part of the spectrum of 'Autoimmune (Auto-inflammatory) Syndrome induced by Adjuvants' (ASIA): analysis of 93 cases.

OBJECTIVES: In this study we analyzed the clinical and demographic manifestations among patients diagnosed with immune/autoimmune-mediated diseases post-hepatitis B vaccination. We aimed to find common denominators for all patients, regardless of different diagnosed diseases, as well as the correlation to the criteria of Autoimmune (Auto-inflammatory) Syndrome induced by Adjuvants (ASIA). PATIENTS AND METHODS: We have retrospectively analyzed the medical records of 114 patients, from different centers in the USA, diagnosed with immune-mediated diseases following immunization with hepatitis-B vaccine (HBVv). All patients in this cohort sought legal consultation. Of these, 93/114 patients diagnosed with disease before applying for legal consultation were included in the study. All medical records were evaluated for demographics, medical history, number of vaccine doses, peri-immunization adverse events and clinical manifestations of diseases. In addition, available blood tests, imaging results, treatments and outcomes were recorded. Signs and symptoms of the different immune-mediated diseases were grouped according to the organ or system involved. ASIA criteria were applied to all patients. RESULTS: The mean age of 93 patients was 26.5 ± 15 years; 69.2% were female and 21% were considered autoimmune susceptible. The mean latency period from the last dose of HBVv and onset of symptoms was 43.2 days. Of note, 47% of patients continued with the immunization program despite experiencing adverse events. Manifestations that were commonly reported included neuro-psychiatric (70%), fatigue (42%) mucocutaneous (30%), musculoskeletal (59%) and gastrointestinal (50%) complaints. Elevated titers of autoantibodies were documented in 80% of sera tested. In this cohort 80/93 patients (86%), comprising 57/59 (96%) adults and 23/34 (68%) children, fulfilled the required criteria for ASIA. CONCLUSIONS: Common clinical characteristics were observed among 93 patients diagnosed with immune-mediated conditions post-HBVv, suggesting a common denominator in these diseases. In addition, risk factors such as history of autoimmune diseases and the appearance of adverse event(s) during immunization may serve to predict the risk of post-immunization diseases. The ASIA criteria were found to be very useful among adults with post-vaccination events. The application of the ASIA criteria to pediatric populations requires further study.

Superior vena cava syndrome - changing etiology in the third millennium.

Superior vena cava syndrome (SVCS), is diagnosed following different degrees of central venous system obstruction, which traditionally was caused by infections, tumors or fibrosing mediastinitis. Recently the role of SVC thrombosis secondary to indwelling central venous devices or pacemaker leads as well as different hypercoagulable states have drawn much attention. In the current review we present a 58-year-old female patient who underwent recurrent pacemaker replacements due to recurrent infections. The patient was hospitalized with superior vena cava syndrome and multiple thrombi in the upper body circulation. Additionally the evaluation was conducted for thrombophilia, which revealed the presence of high titers of antiphospholipid antibodies, suggesting the concurrent diagnosis of the antiphospholipid syndrome (APS). This case reflects the changes in the etiology of SVCS, and the need for a comprehensive evaluation of patients, in the search for additional factors that may complicate a pacemaker insertion, such as the presence of antiphospholipid antibodies. We review the relevant literature and highlight the importance for an interdisciplinary approach in the treatment of SVCS nowadays.

Plasticity in cortical motor upper-limb representation following stroke and rehabilitation: two longitudinal multi-joint FMRI case-studies.

Motor dysfunction and recovery following stroke and rehabilitation are associated with primary motor cortex plasticity. To better track these effects we studied two patients with sub-acute sub-cortical stroke causing hemiparesis, who underwent an effective behavioral treatment termed Constraint Induced Movement Therapy (CIMT). The therapy involves 2 weeks of intensive motor training of the hemiparetic limb coupled with immobilization of the unaffected limb. The study included a longitudinal series of clinical evaluations and fMRI scans, before and after the treatment. The fMRI task included wrist, elbow, or ankle movements. Activity in the M1 upper-limb region of control subjects was stable, strictly contralateral, and similar in amplitude for elbow and wrist movements. These findings reflect the well-known contralateral motor control and support the idea of overlapping representations of adjacent joints in M1. In both patients, pre-CIMT activation patterns in M1 were tested twice and did not change significantly, were contralateral, and included elbow-wrist differences. Following CIMT, the clinical condition of both patients improved and three fMRI-explored prototypes were found: First, cluster position remained constant; Second, ipsilateral activity appeared in the unaffected hemispheres during hemiparetic movements; Third, patient-specific elbow-wrist inter and intra hemispheric differences were modified. All effects were long-lasting. We suggest that overlapping representations of adjacent joints contributed to the cortical plasticity observed following CIMT. Our findings should be confirmed by studying larger groups of homogeneous patients. Nevertheless, this study introduces multi-joint imaging studies and shows that it is both possible and valuable to carry it out in stroke patients.

Multi-center evaluation of autoantibodies to the major ribosomal P C22 epitope.

Anti-ribosomal P (Rib-P) autoantibodies have been demonstrated to be a specific diagnostic marker for systemic lupus erythematosus (SLE). The aim of this study was to evaluate the prevalence of anti-Rib-P (C22) antibodies in patients with SLE drawn from international, multi-center clinics. Sera collected from patients with SLE (n = 333) and various controls (n = 397) in four centers were tested for anti-C22 autoantibodies by ELISA (Dr. Fooke Laboratorien). SLE activity index 2000 (SLEDAI-2K) was assessed for each patient in two centers. Autoantibody profiles were generated for the SLE samples from Canada using two profile assays. Using the manufacturer`s cut-off value, the prevalence of anti-C22 autoantibodies in patients with SLE between the participating centers varied from 18.2 to 29.0%. In the control sera, the prevalence of anti-C22 autoantibodies was low and the titer in the individual control groups varied significantly. In patients with connective tissue disease other than SLE and in patients with infections disease, the anti-C22 reactivity was significantly higher than in healthy controls (P < 0.0001). Overall sensitivity/specificity was 23.1/99.0%, respectively. Anti-Rib-P reactivity was significantly higher in young (mean age 33.9 vs. 45.3 years) SLE patients (P < 0.0001) and was associated with decreased C3 (P = 0.0335) and C4 levels (P = 0.0129). Moderate association between anti-C22 reactivity and SLEDAI-2K was observed in one cohort (P = 0.02). Anti-C22 autoantibodies are frequently and specifically found in patients with SLE. Although an association between anti-C22 reactivity and SLEDAI score was observed in one center, measurement of anti-C22 autoantibodies is likely not appropriate for measuring global disease activity.