Autoimmunity Reviews 8 (2008) 170–175

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Autoimmunity Reviews

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Assessment of systemic vasculitis

Anne Miller a, Neil Basu b, Raashid Luqmani c,⁎a Nuffield Orthopaedic Centre, Oxford, United Kingdomb University of Aberdeen, United Kingdomc Biomedical Research Unit, Botnar Research Centre, University of Oxford, United Kingdom

a r t i c l e i n f o

Abbreviations: ACE, Angiotensin converting enzymantibody;BVAS, Birmingham Vasculitis Activity Score;immunosorbent assay;ESR, Erythrocyte sedimentationmetalloproteinase;MPA, Microscopic polyangiitis;MPOemission tomography;PR3, Proteinase 3;RF, Rheumatoinhibitor of metalloproteinase;US, Ultrasound;VDI, Va⁎ Corresponding author. Tel.: +44 1865 738048; fax

E-mail address: Raashid.luqmani@noc.anglox.nhs.u

1568-9972/$ – see front matter © 2008 Elsevier B.V.doi:10.1016/j.autrev.2008.07.001

a b s t r a c t

Article history:Received 14 June 2008Accepted 6 July 2008Available online 29 July 2008

The systemic vasculitides are an uncommon group of autoimmune diseases capable of causingmulti organ failure and death. Current immunosuppressive strategies have substantiallyimproved the outcome, but the natural history of treated disease is unstable, typicallycharacterised by frequent relapses, drug toxicity and an increasing burden of damage. Earlydiagnosis, accurate staging and regular evaluation of disease status are important in themanagement of the vasculitides. Clinical evaluation tools have been developed and provide acomprehensive assessment of patients. Serological markers, especially anti-neutrophilcytoplasm antibody (ANCA), pathology and imaging investigations are a useful addition, butare more valuable in diagnosis rather than monitoring of disease activity. Advances in magneticresonance imaging in large vessel vasculitis have improved our ability to characterise diseaseand may lead to earlier diagnosis and better control in future. Development of new biomarkersis required in vasculitis, and this is likely to advance our understanding as well as themanagement of these complex conditions.

© 2008 Elsevier B.V. All rights reserved.

Keywords:Systemic vasculitisANCABVASVDIImaging

Contents

1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1712. Clinical measurements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 171

2.1. Quality of life assessments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1713. Laboratory investigations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 171

3.1. Imaging . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1733.2. Mri / Mra . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1733.3. Ultrasound . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1733.4. Positron emission tomography (PET) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1733.5. CT and CT angiography. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 174

4. Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 174Take-home messages . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 174References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 174

e;ACR, American College of Rheumatology;ANA, Anti-nuclear antibody;ANCA, Anti-neutrophil cytoplasmCRP, C reactive protein;CSS, Churg–Strauss syndrome;CT, Computerised tomography;ELISA, Enzyme linkedrate;FDG, 18F-fluorodeoxyglucose;GCA, Giant cell arteritis;IIF, Indirect immunofluorescence;MMP, Matrix, Myeloperoxidase;MRA, Magnetic resonance angiogram;MRI, Magnetic resonance imaging;PET, Positronid factor;sELAM-1, soluble endothelial leukocyte adhesion molecule 1;TA, Takayasu's arteritis;TIMP, Tissuesculitis damage index;VDRL, Venereal Disease Research Laboratory test;WG, Wegener's granulomatosis.: +44 1865 738048.k (R. Luqmani).

All rights reserved.

171A. Miller et al. / Autoimmunity Reviews 8 (2008) 170–175

1. Introduction

The systemic vasculitides remains a difficult set of condi-tions to manage. Despite significant reduction in mortality as aresult of standard immunosuppression [1], most patientsexperience poor quality survival characterized by relapse,persisting low grade disease activity and increasing burden ofdamage from disease scarring and toxicity from treatment [2].

A thorough history and examination should supersede allother assessment tools and be repeated regularly. The natureand extent of assessment will vary according to the stage andcourse of the disease. The absence of validated diagnosticcriteria makes the process even more challenging. TheAmerican College of Rheumatology (ACR) produced validatedclassification criteria meant to distinguish between differentforms of vasculitis for research purposes [3]. The frequentmisuse of the ACR criteria as diagnostic criteria led to aprospective study invalidating this practice [4]. A structuredapproach to management should be based on careful diseasestaging and evaluation [5].

Initial evaluation includes a comprehensive clinicalassessment, serological tests, histology wherever possibleand radiology where appropriate in order to confirm thediagnosis [6,7]. There is no single gold standard and nodiagnostic criteria. A combination of the above allows thediagnosis to be made, but there are still delays in making adiagnosis and initiating therapy, with considerable risk tohealth, especially if the kidney is involved [8]. The relation-ship between anti-neutrophil cytoplasm antibodies (ANCA)and Wegener's granulomatosis (WG) or microscopic poly-angiitis (MPA) suggests that ANCA has a pathogenic role, butthe situation is complex [9]. Animal models have showncompelling evidence for the role of myeloperoxidase (MPO)but not for proteinase 3 (PR3) [10,11].

The widespread availability of the ANCA test has resultedin increased recognition of WG and MPA [12], but use of thetest has been indiscriminate resulting in many false positiveswith an ANCA pattern seen on indirect immunofluorescence(IIF), but not confirmed on specific ELISA testing [13]. Thissuggests the need for a gating policy; in other words if aclinician requests an ANCA test, there should be an appro-priate clinical reason for the request, otherwise the testshould not be performed. Common reasons for requesting thetest include the following: patients with known WG, MPA,and CSS or idiopathic necrotizing glomerulonephritis; chronicdestructive disease of the upper airways; pulmonary nodules;subglottic stenosis; pulmonary-renal syndrome; glomerulo-nephritis; vasculitis of the skin with evidence of systemicdisease; mononeuritis multiplex; retro-orbital mass.

For subsequent evaluations, it is effective and practical tomeasure clinical disease status for most patients with smalland medium vessel vasculitis [5]. Whilst these measures areprimarily used during clinical trials, they can also be appliedin daily management of non trial patients [6,7]. In the absenceof a gold standard for disease activity, they are effective andpractical alternatives. By contrast, for large vessel disease suchas Takayasu's arteritis (TA) such evaluations have a morelimited role. Radiological assessment is probably more useful,but less straightforward to undertake and interpret.

For initial diagnosis particular attention should be directedtowards exclusion of mimics and secondary causes. Imaging

can have a role at this stage; for example the use ofechocardiography in diagnosing infective endocarditis. Biopsymaterial is also useful in the diagnostic process, but must beconsidered within the clinical context. Finally, tools such asANCA [14] can provide support for a diagnosis of systemicvasculitis.

Initial disease activity measures have been shown to be ofprognostic value, providing an objective measure of remis-sion, relapse and grumbling disease throughout the diseasecourse. In the long term, disease damage may have the mostrelevance to a patient's health. The vasculitis damage index(VDI) has exemplified a bi-modal accumulation of damage; anearly phase directly attributable to the vasculitis itself, and alate phase related to treatment [5].

2. Clinical measurements

A careful history and detailed examination of the patientswill providemost of the information required tomanagemostpatients with small and medium vessel vasculitis. Detaileddocumentation of these patients can be undertaken usingstructured clinical assessment tools such as the BirminghamVasculitis Assessment Score (BVAS) to record disease activity[5] and the Vasculitis Damage Index (VDI) to record thepresence of non-healing permanent scars as a result of thedisease or its treatment [5]. BVAS records the presence ofactive features of vasculitis in all body systems, providing astructured checklist of common features. For example,routine urinalysis in patients with localised WG can detectthe presence of asymptomatic but potentially life threateningrenal involvement. Similarly, patients with renal WG maysubsequently develop upper respiratory tract features, whichthey may not routinely report to their treating physicianwithout prompting. A list of BVAS items from the most recentversion of BVAS is shown in Table 1. VDI is similar to BVAS inproviding a structured evaluation of co-morbidity not directlyrelated to the presence of active vasculitis. VDI assessment is asimple process and can highlight problems that require non-immunosuppressive therapy, including chronic nasal crust-ing, osteoporotic fractures and hypertension.Whenmanagingthese complex patients, VDI is useful to screen for commonco-morbidities. A list of VDI items is shown in Table 1.

2.1. Quality of life assessments

Systemic vasculitides have considerable morbidity relatedto both inflammation and its treatment. However, little ispublished on the impact of vasculitis on quality of life,function or employment. Patients with moderate to severepain as a result of vasculitis have impaired Short Form-36scores except for mental health, suggesting pain to be a majordeterminant of quality of life in vasculitis as in most otherdiseases [15]. There is no correlation between modified VDIscores and Short Form-36 subscales or other self-reporteddisease-related measures [15]. There is a need to developquality of life outcome measurements in vasculitis.

3. Laboratory investigations

Laboratory investigations support clinical evaluation inthe assessment of vasculitis, and in monitoring progression

Table 1Disease activity and damage items routinely recorded using the most recent version of the Birmingham Vasculitis Activity Score and the Vasculitis Damage Index(adapted from [5])

Disease activity items Disease damage items

General Chest General Peripheral vascular diseaseMyalgia Wheeze Significant muscle atrophy or

weaknessAbsent pulses in one limb

Arthralgia or arthritis Nodules or cavitiesDeforming/erosive arthritis

2nd episode of absent pulses in onelimbFever≥38.0 °C Pleural effusion/pleurisy

Osteoporosis/vertebral collapse Major vessel stenosisWeight loss≥2 kg InfiltrateAvascular necrosis Claudication N3 monthsCutaneous Endobronchial involvementOsteomyelitis Minor tissue lossInfarct Massive haemoptysis/Alveolar

haemorrhage Skin/mucous membranes Major tissue lossPurpuraCardiovascular Alopecia Subsequent major tissue lossUlcer

Loss of pulses Cutaneous ulcers Complicated venous thrombosisGangreneValvular heart disease Mouth ulcers GastrointestinalOther skin vasculitisPericarditis Ocular Gut infarction/resectionMucous membranes/eyesIschaemic cardiac pain Cataract Mesenteric insufficiency/pancreatitisMouth ulcers/granulomataCardiomyopathy Retinal change Chronic peritonitisGenital ulcersCongestive cardiac failure Optic atrophy Oesophageal stricture/surgeryAdnexal inflammation

Abdominal Visual impairment/diplopia RenalSignificant proptosisPeritonitis Blindness in one eye Estimated/measured GFR≤50%Red eye (Epi)scleritisBloody diarrhea Blindness in second eye Proteinuria≥0.5 g/24 hRed eye conjunctivitis/

blepharitis/keratitis Ischaemic abdominal pain Orbital wall destruction End stage renal diseaseBlurred vision Renal ENT NeuropsychiatricSudden visual loss Hypertension Hearing loss Cognitive impairmentUveitis Proteinuria N1+ Nasal blockage/chronic discharge/crusting Major psychosisRetinal vasculitis/retinal vessel Haematuria≥10 rbc/hpf Nasal bridge collapse/septal perforation SeizuresThrombosis/retinal exudates/ Creatinine 125–249 μmol/l Chronic sinusitis/radiological damage Cerebrovascular accidentRetinal haemorrhages Creatinine 250–499 μmol/l Subglottic stenosis (no surgery) 2nd cerebrovascular accident

ENT Creatinine≥500 μmol/l Subglottic stenosis (with surgery) Cranial nerve lesionBloody nasal discharge/nasalcrusts/ulcers and/or granulomata

Rise in creatinineN 30% orcreatinine clearance fallN25%

Pulmonary Peripheral neuropathy

Para nasal sinus involvement Nervous systemPulmonary hypertension Transverse myelitis

Subglottic stenosis HeadachePulmonary fibrosis Other

Conductive hearing loss MeningitisPulmonary infarction Gonadal failure

Sensorineural hearing loss Organic confusionPleural fibrosis Marrow failure

Seizures (not hypertensive)Chronic asthma Diabetes

StrokeChronic breathlessness Chemical cystitis

Cord lesionImpaired lung function Malignancy

Cranial nerve palsyOther

Sensory peripheral neuropathyMotor mononeuritis multiplex

172 A. Miller et al. / Autoimmunity Reviews 8 (2008) 170–175

and treatment. Histological examination is often regardedas a gold standard investigation. A characteristic histol-ogical picture may confirm a diagnosis of vasculitis andexclude other diseases such as malignancy and infection. Itmay also have a role in establishing the cause of furtherdeterioration in the patient's condition, especially in thekidney. It will guide therapeutic decisions by differentiat-ing between disease activity and damage. However, atypical histological appearance only has diagnostic validityin an appropriate clinical context. Practical difficulties mayarise in obtaining an adequate sample and in its inter-pretation. Immuno-labelling provides clarity but an incon-clusive final result is common. For example, 47% of nasal[16] biopsies are non-specific in the context of systemicvasculitis.

The vasculitides commonly exhibit an acute phaseresponse at onset and during relapse. This may be reflectedby a raised erythrocyte sedimentation rate (ESR), C reactiveprotein (CRP), white cell count, platelets and cholestatic liverfunction tests. These markers lack specificity and areparticularly poor in differentiating from infection. Infectioncan only be excluded by a thorough septic screen includingblood cultures. Laboratory investigations identify secondary

vasculitides and vasculitic mimics, for example HIV andhepatitis serology, VDRL, ACE, RF, ANA and an antipho-spholipid screen. Cryoglobulinemic vasculitis is investigatedwith measurement of cryoprecipitates and complement. Themajority of cases are known to be due to hepatitis C [17].Complement consumption is a marker for immune-complexrelated vasculitis. Hepatitis B has an aetiological role in someforms of polyarteritis nodosa [18]. Eosinophilia is a usefulindicator of Churg–Strauss syndrome [19]. Anti-glomerularbasement membrane antibodies are pathognomonic of Good-pasture's syndrome [20].

The discovery of ANCA [14] has assisted in the diagnosis ofa clinically important group of small vessel vasculitides. Twopatterns are identified under IIF; cytoplasmic (cANCA) andperinuclear (pANCA). They are measured by direct enzyme-linked immunosorbent assays (ELISA) and are specific for theneutrophil antigens proteinase 3 (PR3) and myeloperoxidase(MPO) respectively. Generally these combinations correlatewith WG and microscopic polyangiitis MPA. Geographicalvariation has been noted, and other antigens have also beenidentified. The diagnostic value of cANCA in WG varies from66% to 85.5% in active disease, and the specificity is over 95%[21]. There has been limited success in monitoring ANCA

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titres to assess disease activity and treating with immuno-suppressive therapy on the basis of rising titres [22]. However,a rise in ANCA without change in clinical status cannot beused to justify escalation of treatment [23].

Standard investigations are useful in charting diseaseextent and activity, but need to be interpreted in theappropriate clinical context. Anaemia is common and mayreflect chronic disease, but a sudden fall in haemoglobin ina breathless patient suggests pulmonary haemorrhage.Raised creatinine kinase suggests muscle involvement.Abnormal urea and creatinine levels indicate renal involve-ment. Urinary sediment, particularly containing red cellcasts, is often the first sign of renal disease. Proteinuriaalone is a measure of renal damage. Haematuria followingrecent cyclophosphamide therapy may indicate a chemicalcystitis. In long standing disease, it may indicate urothelialcancer, depending on the cumulative exposure [24].Cardiovascular morbidity and reversible risk factors suchas hypercholesterolemia and hyperglycemia should beassessed and treated. High doses of cyclophosphamidemay cause gonadal failure [25] and can be confirmed withFSH/LH levels.

Experimental markers of disease activity have included anumber of biomarkers including von Willebrand factor [26],endothelial cell antibodies [27] and adhesion molecules suchas sELAM-1 [28]. MMP-2 and TIMP-1 urinary enzyme levelshave recently shown to correlate with renal damage in ANCAassociated vasculitis [29].

3.1. Imaging

Imaging has a dual role in the assessment of vasculitis.Firstly it can provide information on the vessel pathology. Thisis mainly available for large vessel vasculitis. Secondly itprovides information on organ damage. A high resolution CTscan of the lungs will provide diagnostic and prognosticinformation inWG and CSS. MRI of the sinuses can be used fordiagnosis and review of upper airway involvement of WG.Wewill focus on the emerging role of imaging in large vesselvasculitis.

For TA the current gold standard for imaging is percutaneousintravascular angiography, since it is not possible to biopsy largevessels unless the patient is undergoing reconstructive arterialsurgery. Angiography is invasive, widely available and providesdata on luminal anatomy, demonstrating stenosis, occlusionand aneurysm. It also provides a means of assessing centralaortic pressures with imaging of the coronary arteries but failsto demonstrate changes in the arterial wall. This could give afalsely reassuring picture in the early stages of disease.Advances in imaging have been made for large vessel vasculitisin magnetic resonance imaging and angiography (MRI/MRA),high resolution ultrasound (US) positron emission tomography(PET) and computed tomography (CT). These newer techniquesare less invasive, and at least for MR and US do not involveionizing radiation. They have the advantage of providinginformation on the vessel wall. The confirmation of vesselinflammation at an earlier and more reversible stage woulddefine a target for immunosuppression in order to preventdevelopment of long term structural damage. However, there isa lack of large prospective studies correlating radiologicalfindings with pathologic features and clinical changes.

3.2. Mri / Mra

Large vessel imaging by MRI has been investigated in TA[30] and in giant cell arteritis [31]. MRI demonstratesincreased vessel wall thickness, oedema, and mural contrastenhancement in early vascular inflammation [30]. Coronaryartery involvement in Takayasu is reported in up to a third ofcases, and detailed imaging is important [32]. High resolutionMRI demonstrates mural inflammation of the superficialcranial arteries in GCA and resolution with clinical remission[31]. This could assist accurate localization of inflamed arterialsegments for biopsy, and provide a non-invasive means ofdiagnosis and follow-up. MRI imaging of all the majorsuperficial cranial arteries has potential for providing amore accurate assessment than isolated temporal arterybiopsy. MRI may also be used to detect aortitis in patientswith GCA.

3.3. Ultrasound

Colour duplex ultrasonography demonstrates vasculitis inGCA by showing the halo sign, stenosis and occlusion [33]. Thehalo sign is defined as a dark area around the vessel lumen dueto arterialwall oedema. Ameta-analysis of test performance ofultrasonography for giant cell arteritis concluded an overallsensitivity of 69% and specificity of 82% of the halo signcompared with temporal artery biopsy [34]. Usefulness ofultrasound depends on the pre-test probability of GCA. A pre-test probability of 10% and negative ultrasound practicallyexclude the disease. The presence of an US halo around thetemporal artery was 82% sensitive and 91% specific fordiagnosis of GCA diagnosed by temporal artery biopsy in aprospective case-control study [35]. Specificity for bilateralhalos was 100%. This would suggest that in clinical GCA withbilateral halo signs, biopsy is not necessary. Resolution of haloswith corticosteroid treatment has been demonstrated in somestudies [33,35]. Unfortunately, ultrasonography is highlyoperator dependent and has been challenged to be no betterthan physical exam in the diagnosis of GCA [36].

3.4. Positron emission tomography (PET)

18F-fluorodeoxyglucose (FDG) PET scans demonstrateincreased glucose uptake by any cells. This includes inflam-matory cells in diseased vessel walls, but the technique hasbeen primarily developed in oncology practice to assesstumour spread. PET scans are useful in detecting large vesselinflammation and revealing the distribution of GCA and TA.They reveal inflammation in arteries exceeding 4 mmdiameter but have limited application for smaller vesselssuch as the temporal arteries [37]. A system of visual gradingprovides a means of differentiating atherosclerotic lesionsfrom vasculitic [38]. The role of PET scans beyond initialdiagnosis in untreated disease is limited. They do notdemonstrate damage to vessel walls, and changes to luminalflow, and so remain complementary to other imagingmodalities. They demonstrate response to treatment but arenot predictive of a good response to steroids [37]. Theradiation dose associated with PET CT scans is substantiallygreater than CT scanning and should be considered beforeundertaking the examination.

174 A. Miller et al. / Autoimmunity Reviews 8 (2008) 170–175

3.5. CT and CT angiography

CT is useful for imaging the large vessel involvement of TA.It can be employed in early diagnosis since it allowsevaluation of wall thickness in addition to luminal diameter[39]. CT angiography demonstrates stenosis, occlusions,aneurysms and concentric arterial wall thickening affectingthe aorta and its branches, pulmonary arteries and occasion-ally coronary arteries [40]. Limitations of CT include the needfor iodinated contrast material and ionizing radiation.

4. Summary

Accurate structured evaluation of disease status in sys-temic vasculitis is necessary for rational management, makingbest use of existing potentially toxic therapies, to justify theintroduction and ongoing use of expensive biologic therapiesand to detect and manage co-morbidities. Clinical evaluationmethods are standardised and can be applied in clinicalpractice for most forms of small andmediumvessel vasculitis.For large vessel vasculitis, advances in medical imaging haveresulted in the possibility to evaluate progression of diseaseobjectively, discriminating activity from damage.

Take-home messages

• The BVAS and VDI assessment tools provide comprehensiveevaluation of patients with systemic vasculitis, useful inboth diagnosis and monitoring.

• Discovery of ANCA has led to increased recognition of smallvessel vasculitis.

• ANCA cannot be used in isolation to make a diagnosis or asan indicator of the need to change therapy.

• Diagnosis of vasculitis requires exclusion of mimics; otherautoimmune disease, infection and malignancy.

• Advances in MRI and ultrasound provide greater accuracy inthe imaging of large vessel vasculitis.

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Anti-calcium channels antibodies in type 1 diabetes

Previous studies have demonstrated that autoantibodies to L-typathogenesis of the autonomic dysfunction in the bladder and gasstudy,Wan et al. (J Autoimmun 2008;31:66-72) using four blood swith type 1 diabetes and positive anti-calcium channel antibodiesin a mouse model and observed the effects of intravenous immunochannels antibodies decreased the amplitude of spontaneous colbladder. Interestingly, these alterations were blocked after intravethese antibodies on a IVIg column. In conclusion, this study reinpathogenesis of autonomic dysfunction of type 1 diabetes. In additalso play a role in preventing the emergence of these autoantibod

Thyroglobulin and anti-thyroglobuling for follow-up of thyroid c

Thyroid cells are the only source for thyroglobulin. After thyroidepersistence of differentiated thyroid cancer. However, some falthyroglobulin antibodies. In this line, Phan et al. (Eur J Endocrinoldifferentiated thyroid cancer that had undetectable thyroglobulinout of 94 individuals had persistent/recurrent disease (2 with popersistent undetectable thyroglobulin and its antibody) during ththyroglobulin or anti-thyroglobulin during the follow-up presenteddemonstrate that a negative thyroglobulin or its antibody at the tirecurrent disease, however the presence of these hormone/antibo

Autoimmunity in Common Variable Immunodeficiency

Several autoimmune manifestations, such as rheumatoid arthritis,been described in patients with Common Variable ImmunodeficieS42-S45)has recently reviewed themechanisms of this autoimmunand the consequent immaturity of these cells is an important elemproposed mechanism is related to mutations in the gene encodcyclophilin ligand interactor (TACI). TACI is present onmature B celswitch. Knockoutmice for TACI have B cell hyperplasia, increased impossibility comes from the analysis of B cells from patients with agautoreactives and they may come from a lack of B cell receptors siserum BAFF or APRIL were viewed as leading to or accelerating on

diagnosis of giant cell arteritis of the temporal arteries. Rheumatology2004;43:675–6.

[38] Walter MA, Melzer RA, Schindler C, Muller-Brand J, Tyndall A, NitzscheEU. The value of [18F]FDG-PET in the diagnosis of large-vessel vasculitisand the assessment of activity and extent of disease. Eur J Nucl MedMolImaging 2005;32:674–81.

[39] Park JH, Chung JWM, Lee KW, Park YB, Han MC. CT angiography ofTakayasu Arteritis: comparison with conventional angiography. J VascInterv Radiol 1997;8:393–400.

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pe voltage-gated calcium channels may play a role in thetrointestinal tract of patients with type1 diabetes. In a recentamples from patients with autonomic dysfunction associatedand six healthy controls. They have injected these antibodiesglobulin on this model. The authors found that anti-calciumonic motility. On the contrary, they observed an overactivenous immunoglobulin (IVIg) and also with preabsorption offorced the role of anti-calcium channels antibodies in theion, it brought the hypothesis that antiidiotypic networkmayies in healthy individuals.

ancer

ctomy, the presence of thyroglobulin suggests recurrence orse-negative results may come from the presence of anti-2008;158:77-83) have included 94 patients (15 males) withlevels at the time if iodine ablation. The authors found that 8sitive thyroglobulin, 3 with anti-thyroglobulin, and 3 withe follow-up period of 5-14 years. Interestingly, patients witha shorter disease-free survival period. This studywas able tome of the thyroid ablation is not a predictor for persistent ordy is a good marker for recidive.

systemic lupus erythematosus, thyroiditis, and vitiligo, havency (CVI). Cunningham-Rundles (J Clin Immunol 2008;28:ity. One of them is the depletion of switchedmemory B cells,ent for the maintenance of autoimmune clones. The seconding the transmembrane activator and calcium-modulatingls and its activationpromotes a Tcell response and an isotypemunoglobulin synthesis, and autoimmunity. One additionalammaglobulinemia. Vh regions of these cells are commonlygnaling. For some autoimmune disorders, increased levels ofgoing autoimmunity.