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{{Systemic lupus erythematosus}}
{{Systemic lupus erythematosus}}


{{CMG}}; {{AE}} {{RT}}
{{CMG}}; {{AE}} {{MIR}}


==Overview==
== Overview ==
Laboratory findings consistent with the diagnosis of systemic lupus erythematosus include [[autoantibody]] elevation of [[ANA]], [[anti-dsDNA antibody]], [[anti-SM antibody]], and [[antiphospholipid antibodies]], and a decrease in [[complement]] levels. Nonspecific laboratory findings include mild [[pancytopenia]], elevated levels of [[creatinine]] and [[proteinuria]] due to [[renal failure]] (secondary to [[nephritis]]), elevated levels of [[ESR]] and [[C-reactive protein|CRP]] as [[Acute phase reactant|acute phase reactants]], decreased level of [[Complement|complements]], and positive [[Coombs test|direct Coombs test]].


==Diagnosis==
== Laboratory tests ==
Laboratory findings consistent with the diagnosis of systemic lupus erythematosus include [[autoantibody]] elevation of [[ANA]], [[anti-dsDNA antibody]], [[anti-SM antibody]] and [[antiphospholipid antibodies]]. However, decrease of [[complement]] levels is a common finding in SLE.<ref name="pmid2646863">{{cite journal |vauthors=Tan EM |title=Antinuclear antibodies: diagnostic markers for autoimmune diseases and probes for cell biology |journal=Adv. Immunol. |volume=44 |issue= |pages=93–151 |year=1989 |pmid=2646863 |doi= |url=}}</ref><ref name="pmid23316252">{{cite journal |vauthors=Willitzki A, Hiemann R, Peters V, Sack U, Schierack P, Rödiger S, Anderer U, Conrad K, Bogdanos DP, Reinhold D, Roggenbuck D |title=New platform technology for comprehensive serological diagnostics of autoimmune diseases |journal=Clin. Dev. Immunol. |volume=2012 |issue= |pages=284740 |year=2012 |pmid=23316252 |pmc=3536031 |doi=10.1155/2012/284740 |url=}}</ref><ref name="pmid24864270">{{cite journal |vauthors=Li J, Leng X, Li Z, Ye Z, Li C, Li X, Zhu P, Wang Z, Zheng Y, Li X, Zhang M, Tian XP, Li M, Zhao J, Zhang FC, Zhao Y, Zeng X |title=Chinese SLE treatment and research group registry: III. association of autoantibodies with clinical manifestations in Chinese patients with systemic lupus erythematosus |journal=J Immunol Res |volume=2014 |issue= |pages=809389 |year=2014 |pmid=24864270 |pmc=4017718 |doi=10.1155/2014/809389 |url=}}</ref><ref name="pmid25449682">{{cite journal |vauthors=Yaniv G, Twig G, Shor DB, Furer A, Sherer Y, Mozes O, Komisar O, Slonimsky E, Klang E, Lotan E, Welt M, Marai I, Shina A, Amital H, Shoenfeld Y |title=A volcanic explosion of autoantibodies in systemic lupus erythematosus: a diversity of 180 different antibodies found in SLE patients |journal=Autoimmun Rev |volume=14 |issue=1 |pages=75–9 |year=2015 |pmid=25449682 |doi=10.1016/j.autrev.2014.10.003 |url=}}</ref><ref name="pmid16420554">{{cite journal |vauthors=Miyakis S, Lockshin MD, Atsumi T, Branch DW, Brey RL, Cervera R, Derksen RH, DE Groot PG, Koike T, Meroni PL, Reber G, Shoenfeld Y, Tincani A, Vlachoyiannopoulos PG, Krilis SA |title=International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS) |journal=J. Thromb. Haemost. |volume=4 |issue=2 |pages=295–306 |year=2006 |pmid=16420554 |doi=10.1111/j.1538-7836.2006.01753.x |url=}}</ref><ref name="pmid18075790">{{cite journal |vauthors=Truedsson L, Bengtsson AA, Sturfelt G |title=Complement deficiencies and systemic lupus erythematosus |journal=Autoimmunity |volume=40 |issue=8 |pages=560–6 |year=2007 |pmid=18075790 |doi=10.1080/08916930701510673 |url=}}</ref><ref name="pmid15593352">{{cite journal |vauthors=Benito-Garcia E, Schur PH, Lahita R |title=Guidelines for immunologic laboratory testing in the rheumatic diseases: anti-Sm and anti-RNP antibody tests |journal=Arthritis Rheum. |volume=51 |issue=6 |pages=1030–44 |year=2004 |pmid=15593352 |doi=10.1002/art.20836 |url=}}</ref>


[[Antinuclear antibody]] (ANA) testing and anti-extractable nuclear antigen (anti-ENA) form the mainstay of [[Serology|serologic]] testing for SLE.Several techniques are used to detect ANAs.Clinically the most widely used method is indirect [[immunofluorescence]].The pattern of fluorescence suggests the type of antibody present in the patient's serum.
=== Laboratory changes in SLE: ===


ANA screening yields positive results in many connective tissue disorders and other autoimmune diseases, and may occur in normal individuals. Subtypes of antinuclear antibodies include [[LSm|anti-Smith]] and anti-double stranded [[DNA]] (dsDNA) antibodies (which are linked to SLE) and anti-[[histone]] antibodies (which are linked to drug-induced lupus). Anti-dsDNA antibodies are highly specific for SLE; they are present in 70% of cases, whereas they appear in only 0.5% of people without SLE.<ref name="rahman"/> The anti-dsDNA antibody [[titer]]s also tend to reflect disease activity, although not in all cases.<ref name="rahman"/> Other ANA that may occur in SLE sufferers are [[U1 spliceosomal RNA|anti-U1 RNP]] (which also appears in [[systemic sclerosis]]), SS-A (or anti-Ro) and SS-B (or anti-La; both of which are more common in [[Sjögren's syndrome]]). SS-A and SS-B confer a specific risk for heart conduction block in neonatal lupus.<ref name="pmid14671725">{{cite journal |author=Buyon JP, Clancy RM |title=Maternal autoantibodies and congenital heart block: mediators, markers, and therapeutic approach |journal=Semin. Arthritis Rheum. |volume=33 |issue=3 |pages=140–54 |year=2003 |month=December |pmid=14671725 |doi= |url=http://linkinghub.elsevier.com/retrieve/pii/S0049017203001598}}</ref>
{| class="wikitable"
! style="background: #4479BA; color: #FFFFFF; " |<small><small>Exam type</small></small>
! style="background: #4479BA; color: #FFFFFF; " |Lab exam
! style="background: #4479BA; color: #FFFFFF; " |Result
! style="background: #4479BA; color: #FFFFFF; " |Clinical correlation
|-
| rowspan="4" |<small>Hematology</small>
| style="background: #DCDCDC; " |[[Complete blood count]]
|
* [[Leukopenia]]
* [[Lymphopenia]]
* Mild [[anemia]]
* [[Thrombocytopenia]]
|
* Non-specific
* May be related to constitutional symptoms
|-
| style="background: #DCDCDC; " |[[Serum creatinine]]
|Elevated
|
* Suggestive of [[renal dysfunction]]
|-
| style="background: #DCDCDC; " |[[Amylase]]
| rowspan="2" |Elevated
| rowspan="2" |
* Acute [[pancreatitis]]
|-
| style="background: #DCDCDC; " |[[Lipase]]
|-
| rowspan="2" |<small>Urine</small>
| style="background: #DCDCDC; " |[[Urinalysis]]


Other tests routinely performed in suspected SLE are [[complement system]] levels (low levels suggest consumption by the immune system), [[electrolyte]]s and [[renal function]] (disturbed if the kidney is involved), [[Liver function test|liver enzyme]]s, [[complete blood count]] and recently  By [[proteomics]], we can directly detect [[proteins]] as [[gene]] products as well as their alterations by [[post-translational modification]] and internal abscission which are characteristically observed in proteins.<ref name="pmid19252377">{{cite journal |author=Iizuka N, Okamoto K, Hirohata S, Kato T |title=[Analysis of autoantigens in patients with systemic lupus erythematosus by using proteomic approach] |language=Japanese |journal=Nihon Rinsho Meneki Gakkai Kaishi |volume=32 |issue=1 |pages=43–7 |year=2009 |month=February |pmid=19252377 |doi= |url=http://joi.jlc.jst.go.jp/JST.JSTAGE/jsci/32.43?from=PubMed |issn=}}</ref>
| rowspan="2" |
* [[Hematuria]]
* [[Pyuria]]
* [[Proteinuria]]
* Cellular casts
| rowspan="2" |
* Suggestive of [[renal dysfunction]]
|-
| style="background: #DCDCDC; " |Urine sediment
|-
| rowspan="13" |<small>Serology</small>
| style="background: #DCDCDC; " |[[ANA]]
|Elevated
|
* Positive in virtually all patients with SLE at some time in the course of their disease
|-
| style="background: #DCDCDC; " |Antiphospholipid antibodies
|
* [[Lupus anticoagulant]] (LA)
* [[IgG]] and [[IgM]] [[Anti-cardiolipin antibodies|anticardiolipin (aCL) antibodies]]
* [[IgG]] and [[IgM]] anti-beta2-glycoprotein (GP)
|
* Can be predictive of [[hematologic]] and [[Thromboembolic disease|thromboembolic]] involvement
|-
| style="background: #DCDCDC; " |[[Complement]] levels
|
* C3: Vary between varying between normal to slightly reduced
* C4: Reduced
* CH50: Reduced
|
* Impaired clearance of [[immune complexes]]
* Partial [[complement]] deficiency during disease flare ups
** Mostly due to [[complement]] over consumption
* [[Complement]] activity related to organ damage and [[Phagocytosis|auto-phagocytosis]]  
|-
| style="background: #DCDCDC; " |[[Erythrocyte sedimentation rate|Erythrocyte sedimentation rate (ESR)]]
|Elevated
|
* Non-specific
|-
| style="background: #DCDCDC; " |[[C-reactive protein|C-reactive protein (CRP)]]
|Elevated
|
* Non-specific
|-
| style="background: #DCDCDC; " |Urine protein-to-creatinine ratio
|Elevated
|
* [[Lupus nephritis]]
|-
| style="background: #DCDCDC; " |[[Anti-dsDNA antibody]]
|Elevated
|
* Highly specific for SLE
* As high as 70% of patients
|-
| style="background: #DCDCDC; " |[[Anti-SM antibody|Anti-SM antibodies]]
|Elevated
|
* Highly specific for SLE
* Positive in 30% of patients


Previously, the lupus erythematosus (LE) cell test was not commonly used for diagnosis because those LE cells are only found in 50–75% of SLE cases, and are also found in some people with rheumatoid arthritis, scleroderma, and drug sensitivities. Because of this, the LE cell test is now performed only rarely and is mostly of historical significance.<ref>[http://www.nlm.nih.gov/medlineplus/ency/article/003635.htm NIM encyclopedic article on the LE cell test]</ref>
* Lack sensitivity
|-
| style="background: #DCDCDC; " |Anti-Ro/SSA antibodies
|Elevated
|
* Positive in 30% of patients
* More commonly associated with [[Sjögren’s syndrome]]
|-
| style="background: #DCDCDC; " |Anti-La/SSB antibodies
|Elevated
|
* Positive in 20% of patients
* More commonly associated with [[Sjögren's syndrome|Sjögren’s syndrome]]
|-
| style="background: #DCDCDC; " |Anti-U1 RNP antibodies
|Elevated
|
* Positive in approximately 25% of patients with SLE
* Not specific, always present in patients with [[mixed connective tissue disease]] (MCTD)
|-
| style="background: #DCDCDC; " |Antiribosomal P protein antibodies
|Elevated
|
* High specificity for SLE & low sensitivity for SLE
* Lack specificity for involvement of a particular organ system or disease manifestation
|-
| style="background: #DCDCDC; " |[[Coombs test|Direct Coombs' test]]
|Positive
|
* Clinically important in the absence of other causes of [[hemolytic anemia]]
|}


As a summary:
If the initial ANA test is negative, but the clinical suspicion of SLE is high, then additional antibody testing may still be appropriate. This is partly related to the differences in the sensitivity and specificity among the methods used to detect ANA.


*Medical history
=== Laboratory exams to distinguish SLE from other diseases ===
*Complete physical examination
{| class="wikitable"
*Laboratory tests:
! style="background: #4479BA; color: #FFFFFF; " |Test
:*[[Complete blood count]] ([[CBC]])
! style="background: #4479BA; color: #FFFFFF; " |Interpretation
:*[[Erythrocyte sedimentation rate]] ([[ESR]])
|-
:*Urinalysis
| style="background: #DCDCDC; " |Anti-cyclic citrullinated peptide (CCP) antibodies
:*Blood chemistries
|
:*Complement levels
* In patients with predominant [[arthralgias]] or [[arthritis]] may help exclude a diagnosis of [[Rheumatoid arthritis|rheumatoid arthritis (RA)]]
:*[[Antinuclear antibody|Antinuclear antibody test]] ([[ANA]])
* Higher specificity for [[RA]]
:*Other autoantibody tests (anti-DNA, anti-Sm, anti-RNP, anti-Ro [SSA], anti-La [SSB])
|-
:*[[Anticardiolipin antibody|Anticardiolipin antibody test]]
| style="background: #DCDCDC; " |Rheumatoid factor (RF)
*[[Skin biopsy]]
|
*[[biopsy|Kidney biopsy]]
* Less diagnostic since only 20 to 30 percent of people with SLE have a positive [[RF]]
* Consider [[RA]]
|-
| rowspan="4" style="background: #DCDCDC; " |Serological studies for infection
|
* [[Serologic]] testing for [[Human parvovirus B19 infection|human parvovirus B19]]
** In patients with a brief history (for example, less than six weeks) of predominant [[arthralgias]] or [[arthritis]]
|-
|
* [[Serology|Serologic]] testing for [[Hepatitis|hepatitis B virus (HBV)]] and [[Hepatitis C virus|hepatitis C virus (HCV)]]
** In patients with multi-systemic clinical findings
|-
|
* [[Serology|Serologic]] studies for [[borrelia]]
** Especially in areas endemic for [[lyme disease]]
|-
|
* Testing for [[Epstein-Barr virus|Epstein-Barr virus (EBV)]]
|-
| style="background: #DCDCDC; " |Creatine kinase (CK)
|
* Can reflect [[myositis]] (relatively uncommon in patients with SLE)
* [[Myositis]] may also suggest an alternative diagnosis such as:
** [[Mixed connective tissue disease|MCTD]]
** [[Polymyositis|Polymyositis (PM)]]
** [[Dermatomyositis|Dermatomyositis (DM)]]
|}
 
=== A more detailed look into auto-antibodies in SLE ===
{| class="wikitable"
! style="background: #4479BA; color: #FFFFFF; " |Antibodies
! style="background: #4479BA; color: #FFFFFF; " |Prevalence
! style="background: #4479BA; color: #FFFFFF; " |Association with disease activity
! style="background: #4479BA; color: #FFFFFF; " |Pathogenesis involvement
|-
| style="background: #DCDCDC; " |[[ANA]]
|80
| -
|[[Cutaneous lupus erythematosus]]
|-
| style="background: #DCDCDC; " |dsDNA
|70
| -/+
|[[Lupus nephritis]]
|-
| style="background: #DCDCDC; " |Anti-Sm antibodies
|30
| -
|[[Renal]], [[Neurology|neurologic]], [[vasculitis]] and [[hematologic diseases]]
|-
| style="background: #DCDCDC; " |snRNP (U1 RNP)
|30-40
| -
| -
|-
| style="background: #DCDCDC; " |SSA/Ro
|30
| -
|[[Neonatal lupus]]
|-
| style="background: #DCDCDC; " |SSB/La
|20
| -
|[[Neonatal lupus]]
|-
| style="background: #DCDCDC; " |Antiribosomal P protein antibodies
|20
| -
|[[Neuropsychiatry|Neuro-psychiatric]] disease, [[liver disease]]
|-
| style="background: #DCDCDC; " |RF
|20
| -
| -
|}


==References==
==References==

Latest revision as of 19:55, 2 August 2017

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Mahshid Mir, M.D. [2]

Overview

Laboratory findings consistent with the diagnosis of systemic lupus erythematosus include autoantibody elevation of ANA, anti-dsDNA antibody, anti-SM antibody, and antiphospholipid antibodies, and a decrease in complement levels. Nonspecific laboratory findings include mild pancytopenia, elevated levels of creatinine and proteinuria due to renal failure (secondary to nephritis), elevated levels of ESR and CRP as acute phase reactants, decreased level of complements, and positive direct Coombs test.

Laboratory tests

Laboratory findings consistent with the diagnosis of systemic lupus erythematosus include autoantibody elevation of ANA, anti-dsDNA antibody, anti-SM antibody and antiphospholipid antibodies. However, decrease of complement levels is a common finding in SLE.[1][2][3][4][5][6][7]

Laboratory changes in SLE:

Exam type Lab exam Result Clinical correlation
Hematology Complete blood count
  • Non-specific
  • May be related to constitutional symptoms
Serum creatinine Elevated
Amylase Elevated
Lipase
Urine Urinalysis
Urine sediment
Serology ANA Elevated
  • Positive in virtually all patients with SLE at some time in the course of their disease
Antiphospholipid antibodies
Complement levels
  • C3: Vary between varying between normal to slightly reduced
  • C4: Reduced
  • CH50: Reduced
Erythrocyte sedimentation rate (ESR) Elevated
  • Non-specific
C-reactive protein (CRP) Elevated
  • Non-specific
Urine protein-to-creatinine ratio Elevated
Anti-dsDNA antibody Elevated
  • Highly specific for SLE
  • As high as 70% of patients
Anti-SM antibodies Elevated
  • Highly specific for SLE
  • Positive in 30% of patients
  • Lack sensitivity
Anti-Ro/SSA antibodies Elevated
Anti-La/SSB antibodies Elevated
Anti-U1 RNP antibodies Elevated
Antiribosomal P protein antibodies Elevated
  • High specificity for SLE & low sensitivity for SLE
  • Lack specificity for involvement of a particular organ system or disease manifestation
Direct Coombs' test Positive

If the initial ANA test is negative, but the clinical suspicion of SLE is high, then additional antibody testing may still be appropriate. This is partly related to the differences in the sensitivity and specificity among the methods used to detect ANA.

Laboratory exams to distinguish SLE from other diseases

Test Interpretation
Anti-cyclic citrullinated peptide (CCP) antibodies
Rheumatoid factor (RF)
  • Less diagnostic since only 20 to 30 percent of people with SLE have a positive RF
  • Consider RA
Serological studies for infection
Creatine kinase (CK)

A more detailed look into auto-antibodies in SLE

Antibodies Prevalence Association with disease activity Pathogenesis involvement
ANA 80 - Cutaneous lupus erythematosus
dsDNA 70 -/+ Lupus nephritis
Anti-Sm antibodies 30 - Renal, neurologic, vasculitis and hematologic diseases
snRNP (U1 RNP) 30-40 - -
SSA/Ro 30 - Neonatal lupus
SSB/La 20 - Neonatal lupus
Antiribosomal P protein antibodies 20 - Neuro-psychiatric disease, liver disease
RF 20 - -

References

  1. ↑ Tan EM (1989). "Antinuclear antibodies: diagnostic markers for autoimmune diseases and probes for cell biology". Adv. Immunol. 44: 93–151. PMID 2646863.
  2. ↑ Willitzki A, Hiemann R, Peters V, Sack U, Schierack P, Rödiger S, Anderer U, Conrad K, Bogdanos DP, Reinhold D, Roggenbuck D (2012). "New platform technology for comprehensive serological diagnostics of autoimmune diseases". Clin. Dev. Immunol. 2012: 284740. doi:10.1155/2012/284740. PMC 3536031. PMID 23316252.
  3. ↑ Li J, Leng X, Li Z, Ye Z, Li C, Li X, Zhu P, Wang Z, Zheng Y, Li X, Zhang M, Tian XP, Li M, Zhao J, Zhang FC, Zhao Y, Zeng X (2014). "Chinese SLE treatment and research group registry: III. association of autoantibodies with clinical manifestations in Chinese patients with systemic lupus erythematosus". J Immunol Res. 2014: 809389. doi:10.1155/2014/809389. PMC 4017718. PMID 24864270.
  4. ↑ Yaniv G, Twig G, Shor DB, Furer A, Sherer Y, Mozes O, Komisar O, Slonimsky E, Klang E, Lotan E, Welt M, Marai I, Shina A, Amital H, Shoenfeld Y (2015). "A volcanic explosion of autoantibodies in systemic lupus erythematosus: a diversity of 180 different antibodies found in SLE patients". Autoimmun Rev. 14 (1): 75–9. doi:10.1016/j.autrev.2014.10.003. PMID 25449682.
  5. ↑ Miyakis S, Lockshin MD, Atsumi T, Branch DW, Brey RL, Cervera R, Derksen RH, DE Groot PG, Koike T, Meroni PL, Reber G, Shoenfeld Y, Tincani A, Vlachoyiannopoulos PG, Krilis SA (2006). "International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS)". J. Thromb. Haemost. 4 (2): 295–306. doi:10.1111/j.1538-7836.2006.01753.x. PMID 16420554.
  6. ↑ Truedsson L, Bengtsson AA, Sturfelt G (2007). "Complement deficiencies and systemic lupus erythematosus". Autoimmunity. 40 (8): 560–6. doi:10.1080/08916930701510673. PMID 18075790.
  7. ↑ Benito-Garcia E, Schur PH, Lahita R (2004). "Guidelines for immunologic laboratory testing in the rheumatic diseases: anti-Sm and anti-RNP antibody tests". Arthritis Rheum. 51 (6): 1030–44. doi:10.1002/art.20836. PMID 15593352.

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