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


{{CMG}}; {{AE}}<nowiki> {{MIR}</nowiki>
{{CMG}}; {{AE}} {{MIR}}


== Overview ==
== Overview ==
Laboratory findings consistent with the diagnosis of systemic lupus erythematosus include anemia, leukopenia or lymphopenia, elevated levels of ANA, anti-dsDNA, anti-SM and antiphospholipid, and decrease of complement levels.
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]].


== Laboratory tests ==
== 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>
=== Laboratory changes in SLE: ===
{| class="wikitable"
{| class="wikitable"
!
! style="background: #4479BA; color: #FFFFFF; " |<small><small>Exam type</small></small>
!Lab exam
! style="background: #4479BA; color: #FFFFFF; " |Lab exam
!result
! style="background: #4479BA; color: #FFFFFF; " |Result
!clinical correlation
! style="background: #4479BA; color: #FFFFFF; " |Clinical correlation
!
|-
|-
| rowspan="2" |Hematology
| rowspan="4" |<small>Hematology</small>
|Complete blood count
| style="background: #DCDCDC; " |[[Complete blood count]]
|
|
* Leukopenia
* [[Leukopenia]]
* Lymphopenia
* [[Lymphopenia]]
* Mild anemia
* Mild [[anemia]]
* Thrombocytopenia
* [[Thrombocytopenia]]
| colspan="2" |
|
* Non-specific
* May be related to constitutional symptoms
|-
|-
|Serum creatinine
| style="background: #DCDCDC; " |[[Serum creatinine]]
|Elevated  
|Elevated  
| colspan="2" |
|
* Suggestive of renal dysfunction
* Suggestive of [[renal dysfunction]]
|-
| style="background: #DCDCDC; " |[[Amylase]]
| rowspan="2" |Elevated
| rowspan="2" |
* Acute [[pancreatitis]]
|-
| style="background: #DCDCDC; " |[[Lipase]]
|-
|-
|Urine
| rowspan="2" |<small>Urine</small>
|Urinalysis
| style="background: #DCDCDC; " |[[Urinalysis]]
Urine sediment
 
|
| rowspan="2" |
* Hematuria
* [[Hematuria]]
* Pyuria
* [[Pyuria]]
* Proteinuria
* [[Proteinuria]]
* Cellular casts
* Cellular casts
| colspan="2" |
| rowspan="2" |
* Suggestive of [[renal dysfunction]]
|-
|-
| rowspan="12" |Serology
| style="background: #DCDCDC; " |Urine sediment
|ANA
|-
| rowspan="13" |<small>Serology</small>
| style="background: #DCDCDC; " |[[ANA]]
|Elevated
|Elevated
| colspan="2" |
|
* Positive in virtually all patients with SLE at some time in the course of their disease
* Positive in virtually all patients with SLE at some time in the course of their disease
|-
|-
|Antiphospholipid antibodies
| style="background: #DCDCDC; " |Antiphospholipid antibodies
16420554
|
|
* Lupus anticoagulant [LA]
* [[Lupus anticoagulant]] (LA)
* IgG and IgM anticardiolipin [aCL] antibodies
* [[IgG]] and [[IgM]] [[Anti-cardiolipin antibodies|anticardiolipin (aCL) antibodies]]
* IgG and IgM anti-beta2-glycoprotein [GP]
* [[IgG]] and [[IgM]] anti-beta2-glycoprotein (GP)
| colspan="2" |
|
* aPLs are a heterogenous group of autoantibodies which are directed against phospholipid-binding proteins
* Can be predictive of [[hematologic]] and [[Thromboembolic disease|thromboembolic]] involvement
|-
|-
|complement levels
| style="background: #DCDCDC; " |[[Complement]] levels
18075790
|
|
* C3: vary between varying between normal to slightly reduced
* C3: Vary between varying between normal to slightly reduced
* C4: reduced
* C4: Reduced
* CH50: reduced
* CH50: Reduced
| colspan="2" |
|
* Impaired clearance of immune complexes
* Impaired clearance of [[immune complexes]]
* Impaired handling of apoptotic cells
* Partial [[complement]] deficiency during disease flare ups
* Aberrant tolerance induction or changes in cytokine regulation
** Mostly due to [[complement]] over consumption
* During disease flares, the complement system is activated giving rise to partial deficiency or dysfunction due to consumption
* [[Complement]] activity related to organ damage and [[Phagocytosis|auto-phagocytosis]]
* Takes part in the inflammatory reaction in the diseases which lead to the tissue and organ damage  
:
|-
|-
|Erythrocyte sedimentation rate (ESR)
| style="background: #DCDCDC; " |[[Erythrocyte sedimentation rate|Erythrocyte sedimentation rate (ESR)]]
|Elevated
|Elevated
| colspan="2" |
|
* Non-specific
|-
|-
|C-reactive protein (CRP)
| style="background: #DCDCDC; " |[[C-reactive protein|C-reactive protein (CRP)]]
|Elevated
|Elevated
| colspan="2" |
|
* Non-specific
|-
|-
|Urine protein-to-creatinine ratio
| style="background: #DCDCDC; " |Urine protein-to-creatinine ratio
|Elevated
|Elevated
| colspan="2" |
|
* [[Lupus nephritis]]
|-
|-
|Anti-dsDNA
| style="background: #DCDCDC; " |[[Anti-dsDNA antibody]]
|Elevated
|Elevated
| colspan="2" |
|
* Highly specific for SLE
* Highly specific for SLE
* In 70% of patients
* As high as 70% of patients
|-
|-
|anti-Sm antibodies  
| style="background: #DCDCDC; " |[[Anti-SM antibody|Anti-SM antibodies]]
|Elevated
|Elevated
| colspan="2" |
|
* Highly specific for SLE  
* Highly specific for SLE  
* In 30% of patients
* Positive in 30% of patients


* Lack sensitivity
* Lack sensitivity
|-
|-
|Anti-Ro/SSA antibodies
| style="background: #DCDCDC; " |Anti-Ro/SSA antibodies
15593352
|Elevated
|Elevated
| colspan="2" |
|
* In 30% of patients
* Positive in 30% of patients
* More commonly associated with Sjögren’s syndrome
* More commonly associated with [[Sjögren’s syndrome]]
|-
|-
|anti-La/SSB antibodies
| style="background: #DCDCDC; " |Anti-La/SSB antibodies
15593352
|Elevated
|Elevated
| colspan="2" |
|
* In 20% of patients
* Positive in 20% of patients
* More commonly associated with Sjögren’s syndrome  
* More commonly associated with [[Sjögren's syndrome|Sjögren’s syndrome]]
|-
|-
|Anti-U1 RNP antibodies
| style="background: #DCDCDC; " |Anti-U1 RNP antibodies
15593352
|Elevated
|Elevated
| colspan="2" |
|
* In approximately 25 percent of patients with SLE
* Positive in approximately 25% of patients with SLE
* Not specific, always present in patients with mixed connective tissue disease (MCTD)
* Not specific, always present in patients with [[mixed connective tissue disease]] (MCTD)
|-
|-
|Antiribosomal P protein antibodies
| style="background: #DCDCDC; " |Antiribosomal P protein antibodies
|Elevated
|Elevated
| colspan="2" |
|
* High specificity for SLE & low sensitivity for SLE
* High specificity for SLE & low sensitivity for SLE
* Lack specificity for involvement of a particular organ system or disease manifestation
* Lack specificity for involvement of a particular organ system or disease manifestation
|-
|-
|
| style="background: #DCDCDC; " |[[Coombs test|Direct Coombs' test]]
|Direct Coombs' test
|Positive
|Positive
|
|
* Clinically important in the absence of other causes of hemolytic anemia
* Clinically important in the absence of other causes of [[hemolytic anemia]]
|
|}
|}


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.  
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
=== Laboratory exams to distinguish SLE from other diseases ===
{| class="wikitable"
{| class="wikitable"
!
! style="background: #4479BA; color: #FFFFFF; " |Test
!
! style="background: #4479BA; color: #FFFFFF; " |Interpretation
!
|-
| style="background: #DCDCDC; " |Anti-cyclic citrullinated peptide (CCP) antibodies
|
* In patients with predominant [[arthralgias]] or [[arthritis]] may help exclude a diagnosis of [[Rheumatoid arthritis|rheumatoid arthritis (RA)]]
* Higher specificity for [[RA]]
|-
|-
|anti-cyclic citrullinated peptide (CCP) antibodies
| style="background: #DCDCDC; " |Rheumatoid factor (RF)
|In patients with predominant arthralgias or arthritis may help exclude a diagnosis of rheumatoid arthritis (RA)
higher specificity for RA and may be more useful for distinguishing the arthritis associated with RA. (See "Biologic markers in the diagnosis and assessment of rheumatoid arthritis", section on 'Rheumatoid factors' and "Biologic markers in the diagnosis and assessment of rheumatoid arthritis
|
|
* Less diagnostic since only 20 to 30 percent of people with SLE have a positive [[RF]]
* Consider [[RA]]
|-
|-
|Rheumatoid factor (RF)
| rowspan="4" style="background: #DCDCDC; " |Serological studies for infection
|less diagnostic utility since 20 to 30 percent of people with SLE have a positive RF
|
|
* [[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]]
|-
|-
| rowspan="4" |Serological studies for infection
|
|serologic testing for human parvovirus B19
* [[Serology|Serologic]] testing for [[Hepatitis|hepatitis B virus (HBV)]] and [[Hepatitis C virus|hepatitis C virus (HCV)]]
|In patients with a brief history (for example, less than six weeks) of predominant arthralgias or arthritis
** In patients with multi-systemic clinical findings
|-
|-
|serologic testing for hepatitis B virus (HBV) and hepatitis C virus (HCV)
|
|in patients with multisystemic clinical findings
* [[Serology|Serologic]] studies for [[borrelia]]
** Especially in areas endemic for [[lyme disease]]
|-
|-
|serologic studies for Borrelia
|
|n areas endemic for Lyme disease
* Testing for [[Epstein-Barr virus|Epstein-Barr virus (EBV)]]
|-
|-
|Testing for 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]]
|-
|-
|Creatine kinase (CK)
| style="background: #DCDCDC; " |RF
|may reflect myositis, which is relatively uncommon in patients with SLE.
|20
|Myositis may also suggest an alternative diagnosis such as MCTD, polymyositis (PM), or dermatomyositis (DM).
| -
| -
|}
|}


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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