A 17-Year-Old Female with Systemic Lupus Presents with Complex Movement Disorder: Possible Relationship with Antiribosomal P Antibodies

Complex movement disorder is a relatively rare presentation of neurolupus. Antiphospholipid antibodies are associated with movement disorders likely via aberrant neuronal stimulation. Antiribosomal P antibodies have been previously associated with neuropsychiatric disorders but their correlation with movement disorder was not previously established. Our case report involves a 17-year-old Caucasian female patient positive for only antiribosomal P antibody and lupus anticoagulant who presented with a sudden onset of complex movement disorder. After complete cessation of physical signs with olanzapine, anticardiolipin and anti-β2 glycoprotein I antibodies became positive which indicates a likely discordance between movement disorder and antiphospholipid antibodies. This also indicates a potential causal role of antiribosomal P antibodies in inducing movement disorder.

Download Full-text

Autoantibodies to Phospholipids and to the Coagulation Proteins in AIDS

Thrombosis and Haemostasis ◽

10.1055/s-0038-1656067 ◽

1997 ◽

Vol 77 (05) ◽

pp. 0856-0861 ◽

Cited By ~ 65

Author(s):

N Abuaf ◽

S Laperche ◽

B Rajoely ◽

R Carsique ◽

A Deschamps ◽

...

Keyword(s):

Lupus Erythematosus ◽

Antiphospholipid Antibodies ◽

Blood Donors ◽

Heterogeneous Mixture ◽

Systemic Lupus ◽

Hematological Disorders ◽

False Positive Test ◽

Glycoprotein I ◽

Coagulation Proteins ◽

Hiv 1

SummaryIn HIV-1 infection, an increased prevalence of anticardiolipin autoantibodies (aCL) and lupus anticoagulant (LA) has been described. In order to see if these antibodies are isolated or, like in autoimmune diseases, associated with hematological disorders and with antibodies to other phospholipids and to proteins of coagulation, we investigated 3 groups of patients: 1. 342 HIV-1 infected patients, 2. 145 control patients including 61 systemic lupus erythematosus (SLE) patients, 58 patients with a connective tissue disease, 15 patients with stroke, 11 patients with syphilis and 3.100 blood donors. In HIV-1 infection antiprothrombin (aPrT) antibodies were present in 25% of patients, the prevalence of antiphosphatidylcholine antibodies (aPC) (50%) was almost as high as aCL (64%), and 39% had both antibodies. Absorption on liposomes of the latter revealed an heterogeneous mixture of aCL and aPC or cross-reacting antibodies. In contrast with SLE, anti-β2-glycoprotein I (4%), LA (1%), biological false positive test for syphilis (0.3%), thrombosis (p <0.001) were uncommon. In HIV-1 infection, antiphospholipid antibodies do not associate with features linked to them in SLE or syphilis.

Download Full-text

Atherosclerosis in systemic lupus: The role of antiphospholipid antibodies needs strict diagnostic criteria to be evaluated. Comment on the article by Urowitz et al

Arthritis Care & Research ◽

10.1002/acr.20340 ◽

2010 ◽

Vol 63 (1) ◽

pp. 173-174

Author(s):

Piero Stratta ◽

Paola Mesiano ◽

Andrea Campo ◽

Loredana Colla ◽

Fabrizio Fop ◽

...

Keyword(s):

Diagnostic Criteria ◽

Antiphospholipid Antibodies ◽

Systemic Lupus

Download Full-text

Systemic lupus erythematosus valve disease by transesophageal echocardiography and the role of antiphospholipid antibodies

Journal of the American College of Cardiology ◽

10.1016/0735-1097(92)90368-w ◽

1992 ◽

Vol 20 (5) ◽

pp. 1127-1134 ◽

Cited By ~ 104

Author(s):

Carlos A. Roldan ◽

Bruce K. Shively ◽

Chi Chi Lau ◽

Frank T. Gurule ◽

Erika A. Smith ◽

...

Keyword(s):

Systemic Lupus Erythematosus ◽

Transesophageal Echocardiography ◽

Lupus Erythematosus ◽

Antiphospholipid Antibodies ◽

Valve Disease ◽

Systemic Lupus

Download Full-text

Pathophysiology of β2-glycoprotein I in antiphospholipid syndrome

Lupus ◽

10.1177/0961203310361352 ◽

2010 ◽

Vol 19 (4) ◽

pp. 379-384 ◽

Cited By ~ 17

Author(s):

E. Matsuura ◽

L. Shen ◽

Y. Matsunami ◽

N. Quan ◽

M. Makarova ◽

...

Keyword(s):

Vascular Disease ◽

Antiphospholipid Syndrome ◽

Mechanism Of Action ◽

Antiphospholipid Antibodies ◽

Physiological Role ◽

Therapeutic Strategies ◽

Physiological Functions ◽

Glycoprotein I ◽

The Impact

Since β2-glycoprotein I (β2GPI) was described as the major antigenic target for antiphospholipid antibodies, many studies have focused their attention to the physiological role of β2GPI and anti-β2GPI antibodies on autoimmune-mediated thrombosis. Studies reporting the physiological role of β2GPI have been numerous, but the exact mechanism of action(s) has yet to be completely determined. β2GPI’s epitopes for anti-β2GPI autoantibodies have been characterized, however, not all of the heterogeneous anti-β2GPI antibodies are pathogenic. The pathophysiologic role of β2GPI has been reported in the fields of coagulation, fibrinolysis, angiogenesis, and atherosclerosis. Our understanding of the impact of β2GPI, its metabolites and autoantibodies to β2GPI on these physiological functions may contribute to the development of better therapeutic strategies to treat and prevent autoimmune-mediated atherothrombotic vascular disease. Lupus (2010) 19, 379—384.

Download Full-text

The Frequency of Phospholipid Antibodies in an Unselected Stroke Population

Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques ◽

10.1017/s0317167100033515 ◽

1998 ◽

Vol 25 (1) ◽

pp. 64-69 ◽

Cited By ~ 44

Author(s):

L.M. Metz ◽

S. Edworthy ◽

R. Mydlarski ◽

M.J. Fritzler

Keyword(s):

Ischemic Stroke ◽

Systemic Sclerosis ◽

Antiphospholipid Antibodies ◽

Anticardiolipin Antibodies ◽

Activated Partial Thromboplastin Time ◽

Systemic Lupus Erythematosis ◽

Stroke Patients ◽

Systemic Lupus ◽

Stroke Population

ABSTRACT:Background:Antibodies to cardiolipin and other phospholipids have been associated with recurrent thrombotic events, including stroke.Methods:Over a 16 month period we assessed an unselected cohort of 151 ischemic stroke patients for the presence of antiphospholipid antibodies. Patients with known systemic lupus erythematosis, systemic sclerosis, or Sjogrens Syndrome were excluded. Sera from patients admitted to hospital with a diagnosis of ischemic stroke (n = 151) and from controls (n = 111) assessed during the same period were tested for antiphospholipid antibodies (APLA) using 3 assays; anticardiolipin antibodies (ACA) by ELISA, prolonged activated partial thromboplastin time (APTT), and VDRL.Results:The average age of ischemic stroke cases was 68 years (range 29 to 91) and of controls 63 years (range 29 to 86). The prevalence of APLA detected by at least one of the three methods was 12% for IS cases and 10% for controls. After correcting for known risk factors such as age, gender, diabetes mellitus, heart disease, hypertension, and smoking, the odds ratio for risk of stroke fell to 0.8 (C.I. 0.4 to 1.2).Conclusions:Our findings suggest that APLA may not be an independent risk factor for ischemic stroke in unselected persons who do not have known systemic lupus erythematosis or systemic sclerosis but further evaluation of the role of lupus anticoagulant is indicated.

Download Full-text

The role of clinically significant antiphospholipid antibodies in systemic lupus erythematosus

Reumatismo ◽

10.4081/reumatismo.2016.891 ◽

2016 ◽

Vol 68 (3) ◽

pp. 137 ◽

Cited By ~ 6

Author(s):

M. Taraborelli ◽

M.G. Lazzaroni ◽

N. Martinazzi ◽

M. Fredi ◽

I. Cavazzana ◽

...

Keyword(s):

Systemic Lupus Erythematosus ◽

Multivariate Analysis ◽

Lupus Erythematosus ◽

Antiphospholipid Antibodies ◽

Valvular Disease ◽

Systemic Lupus ◽

Increased Risk ◽

Clinically Significant ◽

Cutaneous Lupus

The objective is to investigate the role of clinically significant antiphospholipid antibodies (aPL) in a cohort of systemic lupus erythematosus (SLE) patients. All SLE patients followed for at least 5 years and with available aPL profile at the beginning of the follow-up in our center were studied. Clinically significant aPL were defined as: positive lupus anticoagulant test, anti-cardiolipin and/or anti- β2Glycoprotein I IgG/IgM >99<sup>th</sup> percentile on two or more occasions at least 12 weeks apart. Patients with and without clinically significant aPL were compared by univariate (Chi square or Fisher’s exact test for categorical variables and Student’s <em>t</em> or Mann-Whitney test for continuous variables) and multivariate analysis (logistic regression analysis). P values <0.05 were considered significant. Among 317 SLE patients studied, 117 (37%) had a clinically significant aPL profile at baseline. Such patients showed at univariate analysis an increased prevalence of deep venous thrombosis, pulmonary embolism, cardiac valvular disease, cognitive dysfunction and antiphospholipid syndrome (APS), but a reduced prevalence of acute cutaneous lupus and anti-extractable nuclear antigens (ENA) when compared with patients without clinically significant aPL. Multivariate analysis confirmed the association between clinically significant aPL and reduced risk of acute cutaneous lupus [p=0.003, odds ratio (OR) 0.43] and ENA positivity (p<0.001, OR 0.37), with increased risk of cardiac valvular disease (p=0.024, OR 3.1) and APS (p<0.0001, OR 51.12). Triple positivity was the most frequent profile and was significantly associated to APS (p<0.0001, OR 28.43). Our study showed that one third of SLE patients had clinically significant aPL, and that this is associated with an increased risk, especially for triple positive, of APS, and to a different clinical and serological pattern of disease even in the absence of APS.

Download Full-text

Role of the MyD88 transduction signaling pathway in endothelial activation by antiphospholipid antibodies

Blood ◽

10.1182/blood-2002-08-2349 ◽

2003 ◽

Vol 101 (9) ◽

pp. 3495-3500 ◽

Cited By ~ 232

Author(s):

Elena Raschi ◽

Cinzia Testoni ◽

Daniela Bosisio ◽

Maria O. Borghi ◽

Takao Koike ◽

...

Keyword(s):

Antiphospholipid Antibodies ◽

Fetal Loss ◽

Endothelial Activation ◽

Nuclear Factor Κb ◽

Dominant Negative ◽

Signaling Cascade ◽

Glycoprotein I ◽

Tnf Α ◽

Factor Α

Antiphospholipid syndrome (APS) is an autoimmune disease characterized by the persistent presence of antiphospholipid antibodies (aPLs) and recurrent thrombosis or fetal loss. The thrombophilic state has been partially related to the induction of a proinflammatory and procoagulant endothelial cell (EC) phenotype induced by anti–β2-glycoprotein I (β2-GPI) antibodies that bind β2-GPI expressed on the EC surface. Anti–β2-GPI antibody binding has been shown to induce nuclear factor-κB (NF-κB) translocation leading to a proinflammatory EC phenotype similar to that elicited by interaction with microbial products (lipopolysaccharide [LPS]) and proinflammatory cytokines (interleukin 1β [IL-1β], tumor necrosis factor α [TNF-α]). However, the upstream signaling events are not characterized yet. To investigate the endothelial signaling cascade activated by anti–β2-GPI antibodies, we transiently cotransfected immortalized human microvascular endothelial cells (HMEC-1) with dominant-negative constructs of different components of the pathway (ΔTRAF2, ΔTRAF6, ΔMyD88) together with reporter genes (NF-κB luciferase and pCMV-β-galactosidase). Results showed that both human anti–β2-GPI IgM monoclonal antibodies as well as polyclonal affinity-purified anti–β2-GPI IgG display a signaling cascade comparable to that activated by LPS or IL-1. ΔTRAF6 and ΔMyD88 significantly abrogate antibody-induced as well as IL-1– or LPS-induced NF-κB activation, whereas ΔTRAF2 (involved in NF-κB activation by TNF) does not affect it. Moreover, anti– β2-GPI antibodies and LPS followed the same time kinetic of IL-1 receptor–activated kinase (IRAK) phosphorylation, suggesting an involvement of the toll-like receptor (TLR) family. Our findings demonstrate that anti–β2-GPI antibodies react with their antigen likely associated to a member of the TLR/IL-1 receptor family on the EC surface and directly induce activation.

Download Full-text

Elevated IgA antiphospholipid antibodies in healthy pregnant women in Sudan but not Sweden, without corresponding increase in IgA anti-β2 glycoprotein I domain 1 antibodies

Lupus ◽

10.1177/0961203320908949 ◽

2020 ◽

Vol 29 (5) ◽

pp. 463-473 ◽

Cited By ~ 4

Author(s):

S Elbagir ◽

N A Mohammed ◽

H Kaihola ◽

E Svenungsson ◽

I Gunnarsson ◽

...

Keyword(s):

Pregnant Women ◽

Rheumatoid Factor ◽

Antiphospholipid Antibodies ◽

Normal Pregnancy ◽

Thyroid Peroxidase ◽

African Origin ◽

Glycoprotein I ◽

Citrullinated Peptide ◽

Time Point

Objective The role of antiphospholipid antibodies (aPL) during apparently normal pregnancy is still unclear. IgA aPL are prevalent in populations of African origin. Our aim was to measure all isotypes of anticardiolipin (anti-CL) and anti–β2 glycoprotein I (anti-β2GPI) in healthy pregnant and non-pregnant women of different ethnicities. Methods Healthy Sudanese pregnant women ( n = 165; 53 sampled shortly after delivery), 96 age-matched Sudanese female controls and 42 healthy pregnant and 249 non-pregnant Swedish women were included. IgA/G/M anti-CL and anti-β2GPI were tested at one time point only with two independent assays in Sudanese and serially in pregnant Swedes. IgA anti-β2GPI domain 1 and as controls IgA/G/M rheumatoid factor (RF), IgG anti–cyclic citrullinated peptide 2 (anti-CCP2) and anti–thyroid peroxidase (anti-TPO) were investigated in Sudanese females. Results Pregnant Sudanese women had significantly higher median levels of IgA anti-CL, IgA anti-β2GPI ( p < 0.0001 for both antibodies using two assays) and IgM anti-β2GPI (both assays; p < 0.0001 and 0.008) compared with non-pregnant Sudanese. IgA anti-CL and anti-β2GPI occurrence was increased among Sudanese pregnant women compared with national controls. No corresponding increase during pregnancy was found for IgA anti-β2GPI domain 1 antibodies. Both IgG anti-CL and IgG control autoantibodies decreased during and directly after pregnancy among Sudanese. Serially followed Swedish women showed no changes in IgA aPL, whereas IgG/M anti-CL decreased. Conclusions IgA aPL are increased in Sudanese but not in Swedish women, without corresponding increase in IgA domain 1. Whether due to ethnicity and/or environmental influences the occurrence of IgA aPL during Sudanese pregnancies, and its clinical significance, is yet to be determined.

Download Full-text