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Antinuclear antibodies predict a higher number of pregnancy loss in unexplained recurrent pregnancy loss

Sakthiswary R, Rajalingam S, Norazman MR, Hussein H

Clin Ter, 2015;166(2):e98-101.
PMID: 25945451 DOI: 10.7417/CT.2015.1827

OBJECTIVE: The etiology of recurrent pregnancy loss (RPL) is unknown in a significant proportion of patients. Autoimmune processes have been implicated in the pathogenesis. The role of antinuclear antibody (ANA) in this context is largely undetermined. In an attempt to address the lack of evidence in this area, we explored the clinical significance of antinuclear antibody (ANA) in unexplained RPL.
MATERIALS AND METHODS: We studied 68 patients with RPL and 60 healthy controls from September 2005 to May 2012. All subjects were tested for ANA by immunofluorescence testing, and a titer of 1: 80 and above was considered positive. We compared the pregnancy outcome between the ANA positive and ANA negative RPL cases.
RESULTS: The incidence of ANA positivity among the cases (35.3%) was significantly higher than the controls (13.3%) (p=0.005). ANA positive cases showed significantly higher number of RPL (p=0.006) and lower number of successful pregnancies (p=0.013) compared to the ANA negative cases . The ANA titre had a significant association with the number of RPL (p<0.05, r=0.724) but not with the number of successful pregnancies (p=0.054).
CONCLUSIONS: ANA positivity predicts a less favorable pregnancy outcome in RPL. Our findings suggest that the ANA titre is a useful positive predictor of the number of RPL. Hence, ANA test is a potential prognostic tool for this condition which merits further research.

Matched MeSH terms: Antibodies, Antinuclear/blood*
Fulltext The occurrence of autoantibodies in sera of healthy pregnant women

Azizah MR, Shahnaz M, Zulkifli MN, Azila MN, Nasuruddin BA

Med J Malaysia, 1997 Mar;52(1):8-11.
PMID: 10968047

Autoantibodies have been known to be detected during pregnancy. The occurrence of autoantibodies during pregnancy was studied in a group of 146 healthy pregnant women from Jan-March 1995. Serum samples were tested for antinuclear (ANA), anti-ds DNA, anti-mitochondrial, anti-smooth muscle and anti-parietal cell antibodies employing the technique of indirect immunofluorescence. Sera from 66 non-pregnant women were used as controls. Among the pregnant group, 2 (1.4%) were found to have ANA positivity in comparison to none in the control group. This difference was found to be not statistically significant. Only 1 (0.7%) was positive for anti-mitochondrial antibody in the pregnant group compared to one in the control group (p > 0.05). However, anti-ds DNA, anti-smooth muscle and anti-parietal cell antibodies were not detected in both groups. All those positive for autoantibodies were in their 2nd trimester. When these cases were followed-up at the end of their pregnancy, none had complicated pregnancies nor infant abnormalities. Our findings suggest that (a) the occurrence of autoantibodies in pregnant women was not significantly different from non-pregnant controls and that (b) maternal autoantibodies did not appear to cause complications during pregnancy or infant morbidity.

Matched MeSH terms: Antibodies, Antinuclear/blood
The prevalence of antinuclear, anti-dsDNA, anti-Sm and anti-RNP antibodies in a group of healthy blood donors

Azizah MR, Azila MN, Zulkifli MN, Norita TY

Asian Pac J Allergy Immunol, 1996 Dec;14(2):125-8.
PMID: 9177827

We studied the prevalence of antinuclear (ANA), anti-double stranded DNA (dsDNA), anti-Sm and anti-RNP antibodies in a group of 93 blood donors (age range: 18-58 years). Antinuclear and anti-ds DNA antibodies were detected by immunofluorescence (IF) using HEp2 cells and Crithidia luciliae as substrates, respectively, while anti-Sm and anti-RNP antibodies were assayed by ELISA. ANA was found in 6.5% while anti-dsDNA antibodies were not detected in any of the subjects. The 98th percentile was used as cut off where values greater than 0.651 for anti-Sm and 0.601 for anti-RNP antibodies were taken to be positive. This gives a frequency of 1.1% for both antibodies. There was no significant association of antibody positivity with sex or race. We conclude that certain autoantibodies are present in low titres in the normal Malaysian Individuals, at a different frequency compared to other studies probably due to genetic, ethic or environmental factors.

Matched MeSH terms: Antibodies, Antinuclear/blood*
Fulltext Immune-mediated necrotizing myopathy (NAM) related to SARS-Cov-2 infection: a case report

Ibrahim A, Ghazali WSW, Misyail A, Najwa L, Khan AH, Amir WM, et al.

BMC Neurol, 2023 Mar 22;23(1):117.
PMID: 36949469 DOI: 10.1186/s12883-023-03170-1

BACKGROUND: There is a growing body of evidence that severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) or COVID-19 infection is associated with the development of autoimmune diseases. A recent systematic review reported that the new-onset autoimmune disorders during or after COVID-19 infection included inflammatory myopathies such as immune-mediated necrotizing myopathies.
CASE PRESENTATION: We described a 60-year-old man diagnosed with COVID-19 infection and later presented with a two-week history of myalgia, progressive limb weakness, and dysphagia. He had a Creatinine Kinase (CK) level of more than 10,000 U/L, was strongly positive for anti-signal recognition particle (SRP) and anti-Ro52 antibody, and a muscle biopsy revealed a paucity-inflammation necrotizing myopathy with randomly distributed necrotic fibers, which was consistent with necrotizing autoimmune myositis (NAM). He responded well clinically and biochemically to intravenous immunoglobulin, steroids and immunosuppressant and he was able to resume to his baseline.
CONCLUSION: SARS-CoV-2 may be associated with late-onset necrotizing myositis, mimicking autoimmune inflammatory myositis.

Matched MeSH terms: Antibodies, Antinuclear/blood
Anti-nucleosome antibodies as a disease activity marker in patients with systemic lupus erythematosus

Suleiman S, Kamaliah D, Nadeem A, Naing NN, Che Maraina CH

Int J Rheum Dis, 2009 Jul;12(2):100-6.
PMID: 20374326 DOI: 10.1111/j.1756-185X.2009.01391.x

AIM: To measure the level of anti-nucleosome antibodies in systemic lupus erythematosus (SLE) patients, to determine the sensitivity and the specificity of these antibodies in the diagnosis of the disease and to evaluate the relationship between the levels of anti-nucleosome antibodies, anti-dsDNA (double-stranded DNA) and SLE disease activity.
METHODS: A cross-sectional study was conducted. All patients attended either a medical specialist clinic or were admitted to the medical wards of Hospital Universiti Sains Malaysia with the diagnosis of SLE (n = 90), other connective tissue diseases (n = 45) or were normal controls (n = 90) within the period from July 2004 until September 2005. They were tested for anti-nucleosome antibodies by enzyme-linked immunosorbent assay and anti-DNA antibodies by immunofluorescence. SLE disease activity was evaluated by SLE disease activity index (SLEDAI) score.
RESULTS: Out of 90 SLE patients, anti-nucleosome antibodies were positive in 47 (52.2%) patients, whereas these antibodies were positive in three (6.7%) patients with other connective tissue diseases. Anti-dsDNA antibodies were positive in 33 (36.7%) SLE patients, whereas these antibodies were positive in four (8.9%) patients with other connective tissue diseases. Anti-nucleosome antibodies were positive in 40 (97.6%) patients with active SLE, whereas these antibodies were positive in seven (14.3%) patients with inactive SLE. Anti-nucleosome antibodies had a stronger correlation than anti-dsDNA antibodies with SLEDAI score. There was a significant association between anti-nucleosome antibodies and disease activity.
CONCLUSION: Anti-nucleosome antibodies test is highly sensitive and specific for the diagnosis of SLE, especially when the anti-dsDNA antibodies are absent. They are additional disease activity markers in the assessment of SLE disease activity.

Matched MeSH terms: Antibodies, Antinuclear/blood*
Fulltext Kikuchi's lymphadenitis (necrotizing lymphadenitis) and systemic lupus erythematosus: a case report

Fernandez SH

Malays J Pathol, 2000 Jun;22(1):25-9.
PMID: 16329534

A 26-year-old Indian lady was admitted for lower abdominal pain, diarrhoea, vomiting, fever and cough. The initial diagnosis was that of peritonitis secondary to ruptured or perforated viscus with lobar pneumonia. On laparotomy, she was found to have necrotizing or Kikuchi's lymphadenitis of the abdominal lymph nodes. The initial two antinuclear antibody (ANA) results came back negative. She was diagnosed to have systemic lupus erythematosus (SLE) when the third sample for ANA came back positive and the double-stranded DNA (dsDNA) antibody test was homogenously positive. This case illustrates a need to be aware that necrotizing lymphadenitis can precede the onset of systemic lupus erythematosus.

Matched MeSH terms: Antibodies, Antinuclear/blood
Fulltext ANA negative (Ro) lupus erythematosus with multiple major organ involvement: a case report

Che Maraina CH, Kamaliah MD, Ishak M

Asian Pac J Allergy Immunol, 2002 Dec;20(4):279-82.
PMID: 12744629

Anti-nuclear antibody (ANA) negative systemic lupus erythematosus (SLE) occurs in about 4-13% of SLE cases. A small group of ANA negative SLE patients with positive anti-Ro antibodies usually present with typical vasculitic skin lesions which can be associated with photosensitivity, renal disease, congenital heart block or neonatal lupus. We present a case of a persistently ANA negative patient who presented with joint pain, rashes, mouth ulcer and alopecia. Clinical diagnosis of systemic lupus erythematosus was made even though ANA was negative. She was started on steroids and went into remission. Later, she developed several episodes of convulsions associated with fever and prominent vasculitic lesions. The patient was also found to have microscopic hematuria, proteinuria, anemia and thrombocytopenia. Renal biopsy showed lupus nephritis class 1B. Due to the prominent skin lesions, we performed anti-extractable nuclear antigens (ENA) antibodies test and anti-Ro turned out to be positive. The final diagnosis was ANA negative SLE (Ro lupus) with cutaneous, renal, musculoskeletal, hematological and cerebral Involvement.

Matched MeSH terms: Antibodies, Antinuclear/blood
Fulltext Increased IL-23R+ Th Cells Population Exhibits Higher SLEDAI-2K Scores in Systemic Lupus Erythematosus Patients

Izati AF, Mohd Shukri ND, Wan Ghazali WS, Che Hussin CM, Wong KK

Front Immunol, 2021;12:690908.
PMID: 34484186 DOI: 10.3389/fimmu.2021.690908

The IL-23/IL-17 axis plays causative roles in the development and progression of systemic lupus erythematosus (SLE). However, it remains unclear if the IL-17RA+ and IL-23R+ T helper (Th) cells populations are associated with the serum IL-17 and IL-23 levels, or with the immunological parameters and disease activities in SLE patients. Herein, we examined the proportion of IL-17RA+ and IL-23R+ Th cells and serum levels of IL-17 and IL-23 in established SLE patients (n = 50) compared with healthy controls (n = 50). The associations of these interleukins and their receptors with immunological parameters [anti-nuclear antibody (ANA), anti-dsDNA antibody, and C-reactive protein (CRP)] and SLE disease activity (SLEDAI-2K scores) in SLE patients were assessed. CD3+CD4+ Th cells of SLE patients demonstrated significantly elevated IL-17RA+ (p = 1.12 x 10-4) or IL-23R+ (p = 1.98 x 10-29) populations compared with the healthy controls. Serum IL-17 levels were significantly lower in SLE patients compared with the healthy controls (p = 8.32 x 10-5), while no significant difference was observed for the IL-23 serum levels between both groups. IL-23R+ Th cells population was significantly associated with higher SLEDAI-2K scores (p = 0.017). In multivariate analysis, the proportion of IL-23R+ Th cells remained significantly associated with higher SLEDAI-2K scores independent of prednisolone intake (p = 0.027). No associations were observed between the interleukin parameters (i.e., IL-17, IL-23, IL-17RA+ Th cells, and IL-23R+ Th cells) with ANA, anti-dsDNA, and CRP status, suggesting that the IL-17/IL-23 axis acts independently of these immunological parameters. In conclusion, our results support that therapeutic inhibition of the IL-23/IL-17 axis receptors on Th cells, particularly IL-23R, is potentially relevant in SLE patients.

Matched MeSH terms: Antibodies, Antinuclear/blood
Fulltext Association of anti-CLIC2 and anti-HMGB1 autoantibodies with higher disease activity in systemic lupus erythematosus patients

Syahidatulamali CS, Wan Syamimee WG, Azwany YN, Wong KK, Che Maraina CH

J Postgrad Med, 2017 9 2;63(4):257-261.
PMID: 28862243 DOI: 10.4103/jpgm.JPGM_499_16

BACKGROUND: Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterized by numerous autoantibodies. In this study, we investigated the presence of anti-chloride intracellular channel 2 (anti-CLIC2) and anti-high mobility group box 1 (anti-HMGB1) autoantibodies in SLE patients (n = 43) versus healthy controls ([HCs] n = 43), and their association with serological parameters (antinuclear antibody [ANA], anti-double-stranded DNA [anti-dsDNA], and C-reactive protein [CRP]) and disease activity using Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score (active or inactive).
SETTINGS AND DESIGN: Case-control study at Rheumatology Clinic of Universiti Sains Malaysia Hospital.
SUBJECTS AND METHODS: The sera of SLE patients and HCs were tested for the presence of anti-CLIC2 and anti-HMGB1 autoantibodies using human recombinant proteins and ELISA methodologies. Other serological parameters were evaluated according to routine procedures, and patients' demographic and clinical data were obtained.
STATISTICAL ANALYSIS: Mann-Whitney U-test, Chi-square test, Fisher's exact test, and receiver operating characteristic analysis.
RESULTS: Anti-CLIC2 autoantibody levels were significantly higher in SLE patients compared to HCs (P = 0.0035), whereas anti-HMGB1 autoantibody levels were not significantly elevated (P = 0.7702). Anti-CLIC2 and anti-HMGB1 autoantibody levels were not associated with ANA pattern, anti-dsDNA, and CRP. Interestingly, SLEDAI score (≥6) was associated with anti-CLIC2 (P = 0.0046) and with anti-HMGB1 (P = 0.0091) autoantibody levels.
CONCLUSION: Our findings support the potential of using anti-CLIC2 autoantibodies as a novel biomarker for SLE patients. Both anti-CLIC2 and anti-HMGB1 autoantibody levels demonstrated potential in monitoring SLE disease activity.

Matched MeSH terms: Antibodies, Antinuclear/blood
Fulltext Puerperal acquired factor VIII inhibitor causing a von Willebrand-like syndrome in a patient with anti-DNA antibodies

Jackson N, Hashim ZA, Zainal NA, Jamaluddin N

Singapore Med J, 1995 Apr;36(2):230-1.
PMID: 7676276

A 30-year-old Malay lady, with no previous or family history of bleeding, presented with severe gum bleeding 25 days post-partum. The factor VIII:c was 0.03 iu/ml with evidence of a slow-acting factor VIII inhibitor. Von Willebrand factor antigen (VWF:age) varied from less that 0.05 to 0.17 iu/ml, and there was absent ristocetin-induced platelet aggregation. Anti-nuclear and anti-DNA antibodies were present, but there were no other features of systemic lupus erythematosus. There was some clinical response to cryoprecipitate and tranexamic acid, and slight improvement with corticosteroid. Fifteen months later, the patient has no active bleeding problem, and her VWF-ag is increasing spontaneously. However, factor VIII:c is less than 0.01 iu/ml and her factor VIII inhibitor titre is still > 20 Bethesda units/ml.

Matched MeSH terms: Antibodies, Antinuclear/blood*
Fulltext Pediatric systemic lupus erythematosus. Retrospective analysis of clinico-laboratory parameters and their association with Systemic Lupus Erythematosus Disease Activity Index score

Nazri SKSM, Wong KK, Hamid WZWA

Saudi Med J, 2018 Jun;39(6):627-631.
PMID: 29915860 DOI: 10.15537/smj.2018.6.22112

OBJECTIVES: To elucidate the clinico-laboratory characteristics associated with pediatric systemic lupus erythematosus (pSLE) patients with higher Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score in a retrospective cohort of pSLE patients.

METHODS: A retrospective study involving 32 pSLE patients was conducted at Hospital Universiti Sains Malaysia, Kelantan, Malaysia between 2006 and 2017.

RESULTS: Within the group of 32 pSLE patients, 23 were girls and 9 were boys (3:1 ratio). The most common symptom was renal disorder (n=21; 65.6%) followed by malar rash (n=9; 28.1%), oral ulcers (n=7; 21.9%), prolonged fever (n=5; 15.6%) and arthritis (n=4; 12.5%). Antinuclear antibodies (ANA) were detected in all patients and 25 patients (78.1%) were positive for anti-double stranded DNA (anti-dsDNA) antibodies. Eighteen (56.3%) patients had active SLE (SLEDAI ≥6), and these patients were significantly associated with heavy pyuria (p=0.004), a high ANA concentration (1:160; p=0.040, 1:320; p=0.006), elevated ESR (p=0.006), low C3 levels (p=0.008), oral ulcers (p=0.010), heavy hematuria (p=0.017) and heavy proteinuria (p=0.017), lupus erythematosus (LE)-nonspecific lesion manifestations (p=0.019) and malar rash (p=0.044).

CONCLUSION: Pediatric systemic lupus erythematosus patients with higher SLEDAI score were most significantly associated with pyuria, high ANA titers, and elevated ESR.

Matched MeSH terms: Antibodies, Antinuclear/blood*

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