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Descriptive study, cross-sectional, longitudinal follow-up comparisons and post-treatment to evaluate treatment outcomes. collection patients convenience over time.

Descriptive study, cross-sectional, longitudinal follow-up comparisons and post-treatment to evaluate treatment outcomes. collection patients convenience over time.

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6

2.2.3.6. Tests for the cytokines TFNA, IL6, IL10

2.2.4. Treatment regimen

Pulse MP therapy: Patients were treated with 1 g

methylprednisolone (MP) / day as recommended by the American

Rheumatology Association, which was administered for 3 consecutive

days. Methylprednisolone 1 g diluted in 100 ml sodium and infusion

intravenous for 1 hour, the patient is monitored by monitor. Patients are

closely monitored clinically: pulse, heat, blood pressure, weight, urine /

24 hours, monitoring of cardiac, pulmonary, digestive and full status.

Management of side effects may occur during and after pulse MP.

Treatment basic: After MP therapy, patients continued to receive

Methylprednislone 1mg / kg / day orally, Hydoxychloroquine, and other

medications: hypotension, calcium-D, potassium supplementation. ,

medications for symptomatic relief and other prophylaxis if needed.

Evaluate the response to treatment and follow-up of side effects at the

time of the visit according to the study sample.

2.2.5. Result evaluation

 Evaluation of immune dysfunction in 112 severe SLE patients

 Evaluation of treatment response based on changes in anti-dsDNA

antibody levels before and after treatment for 1 week, 4 weeks and

12 weeks.

 Evaluation of treatment response based on changes in C3, C4, Ig

MD before and after MP treatment 1 week, 4 weeks and after 12

weeks.

 Evaluation of treatment response was based on changes in cytokine

TNFA, IL6, IL 10 before and after MP treatment for 1 week and 4

weeks.

 Overall treatment response was based on SLEDAI changes before

and after treatment at 1 week, 4 weeks and 12 weeks, and divided

the response based on SLEDAI score of decline according to ACR .







For lupus nephritis with syndrome nephrotic , we evaluated the

response based on the Kedney Disease Improving Global Outcomes

(KDIGO 2012) guidelines as follows: Complete response:

Proteinuria <0, 5 g / 24h, blood albumin ≥ 3 g / dL, GFR> 60 ml /

min or improvement of eGFR> 50% vs. pretreatment, no red blood

cell, urolith. Partial response: Reduction in creatinine clearance>

50% vs. pretreatment, blood serum albumin <3 g / dL and



7

improvement of eGFR> 50% vs. pretreatment. Not responding: 

Proteinuria> 3g / 24h, decreased urinary protein <50% compared

with before treatment, reduced eGFR <20% compared with pretreatment.

2.2.7. Study diagram



Clinical examination, tests and selection

Patients are eligible critica for study



112 severe SLE



Characteristics of immune

disorders - Related analysis



80 patients treated with pulse MP



Evaluation of pulse MP therapy efficacy

after 1 week



Evaluation of pulse MP therapy efficacy

after 4 weeks



Evaluation of pulse MP therapy efficacy

after 12 weeks



Report on study results



8

CHAPTER 3- RESULTS OF THE STUDY

3.1. Distribution of patients by age and sex

The highest rates of patients in the age group of 20-29 years,

accounting for 45.5%, for the age group of 20-39 years, accounting for

68.2%, the majority femele accounting for 90.2%

3.2. Characteristics of immune disorders in severely SLE, associated

with some immunological indices with organ damage and

with the SLEDAI score.

3.2.1. Characteristics of immune disorders in severely SLE

3.2.1.1. Characteristics of autoimmune antibodies

Table 3.1. Characteristics of autoimmune antibodies

Autoimmune

antibodies (+)



Number of patients

(n=112)



Ratio %



ANA



110



98.2



Anti-dsDNA



89



79.5



Anti -Sm (n= 103)



44



42.7



Anti-Cardiolipin IgM (n=103)



7



6.8



Anti-Cardiolipin IgG (n=103)



28



27.2



Anti-SSA (Ro) (n=102)



52



51.0



Anti-SSB (La) (n=100)



13



13.0



The rate of ANA (+) was 98.2%, anti-dsDNA (+) was 79.5%,

anti-Sm was 42.7%.



9

3.2.1.2. Characteristics of complements levels and immunoglobulins

levels

Table 3.2. Characteristics of the complements levels and

immunoglobulins levels

Index immunoglobulins

Number of patients

Ratio %

(n=112)

C3 reduction (n=112)

106

94.6

C4 reduction (n=112)



71



63.4



IgA increase (n=109)

IgE increase (n=95)



9

76



8.3

80.0



IgG increase (n=109)

28

25.7

IgM increase (n=109)

10

9.2

C3 decrease rate was 94.6%, C4 decrease was 63.4%, IgE increased

80%

3.2.1.3. Characteristics of cytokine levels

Table 3.3. Characteristics of cytokine levels

Cytokine

Number of

Ratio %

Pg/mL

patients

(n=112)

TNFA

Increase

38

40.4

Medium (min-max)

IL6



Increase

Medium (min-max)



IL10



Increase

Medium (min-max)



25.69 ± 67.45 (1.5 – 506)

90



95.7



53.16 ± 155.14 (0.43 – 1495)

80



85.1



24.64 ± 154.36 (0.02 – 1496)



TNFA increased 40.4%, IL6 increased 95.7% and IL10 increased 85.1%.

3.2.2. Relate some of the immunity indicators and organ damage

3.2.2.1. Autoimmune antibodies and organ demage

3.2.2.1.1. Autoimmune antibodies and kidney lesion



10

Table 3.4. Comparison of serum antibodies levels between the presence

and absence of kidney lesion

Kidney lesion

[Median (quartile)]



Antibodies



Have (n=86)

240.0 (78.63240.0)



Anti-dsDNA UI/mL (n=112)



P

Value



Are not

(n=26)

210.1(60.45240)



0.436



Anti-Cardiolipin IgM U/mL (n=103)



2.0 (2.0-2.98)



4.6 (2.0-6.4)



0.014



Anti-Cardiolipin IgG U/mL (n=103)



5.75 (2.0-21.98)



3.8 (2.8-12.7)



0.833



Anti –Sm UI/mL (n=103)



6.35 (2.63-33.98)



18.8 (5.0-100)



0.021



8.5 (2.1-100)



40.6 (2.8-100)



0.160



Anti-SSA (Ro) UI/mL (n=100)



Anti-SSB (La) UI/mL (n=100)

3.5 (1.1-5.85)

2.5 (1.3-6.2)

The levels of anti-dsDNA were higher in the group with kidney lesion

but not statistically significant.



1



3.2.2.1.2 Autoimmune antibodies and hematologic disorders

Table 3.5. Comparison of autoimmune antibody levels between and

without hematologic disorders

Antibodies



Hematological disorders

[Median (quartile)]

Have (n=90)



Anti-dsDNA UI/mL



240.0 (115.13240.0)



Are not (n=22)



P

Value



59.05(24.95-239.90)



<0.001



Anti-Cardiolipin IgM U/mL



2.0 (2.0-4.6)



2.0 (2.00-3.83)



0.621



Anti-Cardiolipin IgG U/mL



8,3 (2,3-29,6)



2.45 (2.00-3.60)



0.001



Anti –Sm UI/mL

7,0 (2,93-33,98)

18.8 (3.6-100.0)

0.336

Concentration levels of anti-dsDNA and anti-Cardiolipin IgG

were significantly higher (p <0.001 and p = 0.001) in the hematologic

disorder group than in the non-haematological disorder group.



11

3.2.2.3. Relation of cytokine concentrations levels and organ damage

3.2.2.3.1. Cytokine concentrations levels and kidney lesion

Table 3.6. Comparison of cytokine concentrations levels

between kidney lesion group and without kidney lesion

gruop

Cytokine

pg/mL

TNFA (n=94)

IL6 (n=94)

IL10 (n=94)



Kidney lesion

[Median (quartile)]

have (n=86)



Are not (n=26)



9.76 (6.82-17.45)

11.05 (5.41-26.85)



6.53 (4.49-13.86)

17.61 (9.08-45.90)



P Value

0.050

0.221



4.93 (2.88-9.17)

5.01 (3.10-9.17)

0.738

TNFA levels in the kidney lesion group may be higher

3.2.2.3.2. Cytokine levels and hematologic disorders

Table 3.7. Comparison of cytokine levels between and

without hematologic disorders

Hematological disorders

Cytokine

[Median (quartile)]

P Value

pg/mL

have (n=90)

Are not (n=22)

TNFA (n=94)

9.97 (6.81-19.33)

6.42 (4.35-9.22)

0.024

IL6 (n=94)

14.39 (6.25-35.06)

10.25 (3.14-18.26)

0.149

IL10 (n=94)

4.90 (2.87-9.21)

7.08 (3.69-9.12)

0.514

There was a statistically significant difference (p = 0.024) in TNFA

levels between the two groups with haematological disorders and no

haematological disorders.

3.2.2.3.3. Cytokine levels and CNS involvements

Table 3.8. Comparison of cytokine levels between the

presence and absence of CNS involvements

CNS lesions

Cytokine

[Median (quartile)]

p value

pg/mL

have (n=32)

Are not (n=80)

TNFA (n=94)

9.89 (7.58-17.87)

9.19 (6.14-17.04)

0.521

IL6 (n=94)

IL10 (n=94)



18.26 (9.81-34.46)



11.73 (4.83-27.84)



0.192



8.46 (4.69-11.58)



4.54 (2.37-8.51)



0.020



12

There was a statistically significant difference (p = 0.020) in IL10 levels

between the two groups with CNS involvements and no CNS involve.

3.3. Relation of autoimmune antibodies levels, complements,

immunoglobulins, cytokine and disease activity (SLEDAI)

3.3.1. Relation of autoimmune antibodies levels and SLEDAI

3.3.1.1. Relation of autoimmune antibodies levels and SLEDAI

Table 3.9. Relation of autoimmune antibodies levels with

SLEDAI score

SLEDAI

Antibodies



[Median (quartile)]

12-19 points

(n=38)



Anti-dsDNA



117.8 (40.7-240.0)



p value



 20 points (n=74)

240.0 (128.2-240.0)



0.005



Anti-Cardiolipin IgM



2.0 (2.0-4.63)



2.0 (2.0-3.8)



0.494



Anti-Cardiolipin IgG



3.15 (2.0-14.03)



8.0 (2.05-21.95)



0.187



7.5 (3.9-53.9)



7.0 (2.78-54.80)



0.712



Anti -Sm



Anti-dsDNA level were statistically significantly higher (p = 0.005) in

the very active group (SLDAI ≥ 20).

3.3.1.2. Correlation of anti-dsDNA levels and SLEDAI



r = 0.251

p = 0.007



Chart 3.1: Correlation between anti-dsDNA levels and disease activity

(SLEDAI)

Regression equation: SLEDAI = 0.023 x anti-dsDNA + 19.78



13

The level of anti-dsDNA associated with SLEDAI was proportional to

r = 0.251 and p = 0.007.

3.3.2. The average concentration of complement with SLEDAI

3.3.2.1. The average concentration of complements with SLEDAI

Table 3.10. Relation of complement levels with SLEDAI

score

Complement



SLEDAI

12-19 points (n=38)



 20 points

(n=74)



p value



C3 (n=112)



50.15 ± 30.62



34.01 ± 18.19



0.001



C4 (n=112)



12.74 ± 9.11



9.80 ± 6.97



0.059



mg/dL



Mean C3 concentrations were significantly lower in the SLE group and

were significantly associated with a SLEDAI score (p = 0.001).

3.3.2.2. Correlation between complement with SLEDAI

r = -0.267

p = 0.004



Chart 3.4: Correlation between serum levels of C3 and SLEDAI

Regression equation: SLEDAI = -0.093 x C3 + 27.37; C3 concentration

was negatively correlated with the SLEDAI score with

r = -0.093 and p = 0.004.

3.4. Results of pulse PM therapy in severe SLE

3.4.1. Changes of autoimmune antibodies levels



14

Table 3.11. Characteristics of changing anti-dsDNA levels



Anti-dsDNA

UI/mL

Increase ≥

50 UI

Median

(Quartiles)

min - max



after treatment



p value



Before

treatment



1W



4W



12 W



(n=80)

n%



(n=80)

n%



(n=80)

n%



(n=79)

n%



63 (78.8)



p0-1



p0-2



p0-3



43 (53.8) 31 (38.8) 23 (29.1) <0.001 <0.001 <0.001



240.0

(65.2240.0)



52.3

(20.322.6)



36.4

(16.480.4)



26.6

(14.354.3)



<0.001 <0.001 <0.001



3.29 –

0.85 –

0.79 –

240

240

137.6

The rate of anti-dsDNA (+) and anti-dsDNA levels decreased after

treatment for 1 week, 4 weeks and 12 weeks

3.4.2. Caracteristics of change C3, C4 and immunoglobulins levels

Table 3.12. Changes in C3, C4 and immunoglobulins

levels



Index

mg/dL



4.9 – 240



after treatment



P value



Before

treatment



1w



4w



12 w



(n=80)



(n=80)



(n=80)



(n=79)



79.54 ±

23.32



55.40 ±

22.19



p0-1



p0-2



p0-3



90.23 ±

20.27



<0.001



<0.00

1



<0.001



C3



41.67 ±

25.27



C4



10.95 ±

7.86



13.53 ±

7.48



18.84 ±

9.02



20.75 ±

10.10



<0.001



<0.00

1



<0.001



IgA



246.24 ±

103.30



206.32 ± 207.82 ±

83.60

80.01



225.18 ±

83.19



<0.001 0.001



0.091



IgE



545.17 ±

587.51



353.92 ± 366.26 ±

468.08

721.44



188.61 ±

214.94



0.001



0.052



<0.001



IgG



1170.72 ± 943.86 ± 944.76 ± 1007.95 ±

611.70

526.55

402.17

359.58



<0.001



<0.00

1



0.023



IgM



132.16 ±



0.005



0.173



0.786



104.75 ± 115.78 ±



129.52 ±



15

after treatment

P value

Before

treatment

101.27

59.87

61.79

53.23

Increased C3, C4 levels, decreased immunoglobulins levels

after treatment 1 week, 4 weeks and 12 weeks

3.4.3. Changes in cytokine levels

Table 3.13. Cytokine change before and after treatment



Index

mg/dL



Cytokine

pg/mL

Increased

TNFA

Median

Increased

IL6

Median

Increased

IL10

Median



Before

treatment



After treatment



n%



1 tuần- n %



4 tuần - n %



28 (42.4)



20 (32.8)



9 (15.8)



9.40 (6.4217.52)



8.26 (4.9214.72)



6.72 (4.788.77)



64 (97.0)



58 (95,1)



55 (96.5)



10.37 (4.6223.46)



10.47 (4.6120.01)



7.44 (3.3413.36)



56 (84.8)

4.89(3.058.44)



54 (88.5)

4.23 (2.69-6.81)



P value

p0-1



p0-2



0.052 <0.001



0.621



0.026



0.036



0.036



44 (77.2)

3.21 (2.127.16)



IL-10 was significantly reduced after 1 week of treatment (p =

0.036). Increases in TNFA, IL6, IL10 and TNFA, IL6, IL10 levels were

significantly reduced after 4 weeks of treatment



16

3.4.4. Evaluation of overall treatment response across the SLEDAI

Score

Table 3.14. Comparison of SLEDAI score before and after

treatment



SLEDAI



12 points



19



Before

treatm

ent



1w



4w



12 w



(n=80)

n%



(n=80)

n%



(n=80)

n%



(n=79)

n%



after treatment



P value



28 (35.0) 71 (88.8) 79 (98.8) 79 (100)



≥ 20 points 52 (65.0) 9 (11.3)



1 (1.3)



0



Mean



8.63

± 4.58



6.85

± 3.83



23.33

± 8.04



14,03

± 6.43



p0-1



p0-2



p0-3



<0,001



<0,001



<0,001



<0.001



<0.001



<0.001



(min -max)



12-49

2-42

0-29

0-18

SLEDAI score in both high and very active groups were

reduced by one week, after 4 weeks and after 12 weeks of treatment. The

mean score of SLEDAI was decreasing over time: before treatment was

23.33 ± 8.04, after 1 week it was reduced to 14.03 ± 6.43, after 4 weeks

8.63 ± 4.58 and after 12 weeks week 6.85 ± 3.83 points.

3.4.5. Evaluation of treatment response for lupus nephritis with

nephrotic syndrome

Table 3.15. Treatment response level of patients with

nephrotic syndrom

Response

after 1 w

After 4 w

After 12 w

P value

(n=47)

(n=47)

(n=47)

Completely



0



3 (6.4%)



9 (19.1%)



partian



15 (31.9%)



24 (51.1%)



33 (70.2%)



Not responding



32 (68.1%)



20 (42.6%)



5 (10.6%)



<0.001



After 1 week: no patients completely responsive, 31.9% partian

responsive, 68.1% not responsive. After 4 weeks: 6.4% completely

responsive, partian 51.1%, not responding 42.6%. After 12 weeks:

completely responsive 19.1%, partial 70.2%, not responding 10.6%



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Descriptive study, cross-sectional, longitudinal follow-up comparisons and post-treatment to evaluate treatment outcomes. collection patients convenience over time.

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