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View Full Version : hi! possible sle, but negative ANA... questions.



anilla
06-15-2011, 02:50 PM
Hi everyone. I'm glad i found these forums. :)

it appears i am a bit of a medical mystery at the moment. (where is dr. house?!!)

long story short-- i feel like i have most of the symptoms for SLE. but--my blood work is negative, even my ANA, which had been borderline positive last year (it was 40).

what i do know i have for sure are very low IGg A (21) and M (10), and low IGg (~500).

my immunologist doesn't want to diagnose me with a primary immune deficiency. The rheumatologist probably won't want to dx me with sle. meanwhile i feel awful all the time. lately, my joints are killing me, as is this other pain i have in my extremities-- which i can't really describe other than saying it feels like my flesh hurts like a bruise.

i am becoming more and more sensitive to sunlight, to the point where an hour in the sun will leave me exhausted. not to mention cognitive problems, concentration problems, and feeling in a fog constantly.

so i wonder if any of you have experience with diagnoses difficulties. i mean, not that i *want* to have lupus, but i would like to have *something* so that they can start treating and helping me already!

gkf109
06-15-2011, 03:43 PM
I can relate to your story, because what your describing is the same situation I am in, I know exactly how you feel, keep going to your doctor, tell them all your symptoms, keep a daily journal of your symptoms, give it to your doctor, not the nurse, hand it to your doctor, I got a rash on my face, that was there for months, and when I finally went to the doctor they did a biopsy and told me I had tumid lupus, and it would only affect my skin, but I have all the symptoms of SLE, but it doesn't show in my blood either, but they told me my proteins were elevated? I really new nothing about lupus before I had heard the word but knew nothing about it, after I started to research it I couldn't believe all the problems that it caused, but as I was reading it It was me! As dumb as this sounds all the problems I have I just thought everybody felt like this, Good Luck and keep going to your doctor

Peridot20_Gem
06-15-2011, 04:02 PM
Hi Anilla,

A nice warm welcome to WHL and nice to have you with us, there's so many threads to venture through and learn from.

Anilla your symptoms sound linked to lupus and although your ANA was border line last year and as now showed negative, lupus itself is terrible for fluctuating the bloods, so some of your tests which may have come negative many be false readings as this is what Lupus does, there's so many member's still having bloods done constantley till they're diagnosed properly.

If your becoming sensitive to sunlight i suggest you sit in the shade and not for so long because the sun and rays can cause Rashes besides a bad Flare, i can't go in it at all no more because it destroys my skin.

I have Al Diseases overlapping Autoimmune Diseases and the difference it's done to my life is so unbelieveable.

Your best using 50 block when out some member's use 100 and cover yourself best as possible besides hats and sunglasses it may sound extreme but it's better than harming your skin.

Concentration and the foggy brain is a major isssue with Lupus with either Al Diseases or Autoimmune Diseases.

((Hugs Terry)) xxx

lovedbyHim
06-15-2011, 04:06 PM
HI Anilla, welcome to a safe place to feel validated. I was and am borderline with speckled ANA. I am diagnosed with lupus because of all the organs and systems hit. Recently my skin and muscles are tender and going in to terrible spasms. We are looking at possible fibromialgia. I spent many humiliating years with docs who did not diagnose me sufficiently. I had many indicators. I finally found someone who knew her stuff. Yes, document everything. Take pictures of before and after sun exposure. I will try to post a picture of me after exposure. Read everything you can to take charge of your medical care. You know when things aren't right with you. Bless you on this journey. You have a great group of folks walking beside you here.

Peridot20_Gem
06-15-2011, 04:39 PM
Anilla, I'm adding below info on very low IGg A (13) and M (21), and low IGg (~500). as this may help in some way.

Causes of subclass Deficiencies and complete deficiency of individual IgG subclasses may have several consequences:

IgG1: IgG1 deficiencies often result in a decreased level of total IgG (hypogammaglobulinemia). A deficiency of this quantitatively most important subclass is often associated with recurrent infections and might occur in combination with (individual) deficiencies of other subclasses, e.g. IgG3 (36,64). In a recent evaluation of IgG1 concentrations in adults (n=1175) with suspected IgG subclass abnormalities, decreased IgG1 level were observed in 28% of the individuals (table IV).
Read et al. reported IgG1 subclass deficiencies in patients with chronic fatigue syndrome, whereas all other immunoglobulin isotypes were normal (65).
IgG1 deficiency is often associated with Common Variable ImmunoDeficiency.


IgG2: An IgG2 deficiency is offten associated with otitis media acuta and sinusitis, association with ataxia telangietasia and with System Lupus Erythematosus (SLE) has also been reported.
In about half of all IgG subclass deficiencies the IgG2 concentrations are decreased. An isolated IgG2 deficiency is associated with decreased responses to infections with encapsulated bacteria and after immunisation with polysaccharide antigens (38,66). These patients show recurrent respiratory tract infections with pneumococci and/or Haemophilus influenza type B (67,68,69). Low concentrations of IgG2 often occur in association with a deficiency in IgG4 and IgA.

IgG3: Along with IgG1, the IgG3 subclass is most frequently present in the antibody response to protein antigens. IgG3 deficiency has been associated with a history of recurrent infectious, leading to chronic lung disease. Decreased IgG3 levels are frequently associated with IgG1 deficiency (63).

IgG4: An IgG4 deficiency is difficult to assess. In healthy children, IgG4 may have very low concentrations. Methods that are used to measure IgG4 levels have not always been sensitive enough to distinguish complete absence of IgG4 from low-normal IgG4 levels. Thus, in most studies the assessment of IgG4 deficiency is hampered by the high frequency of undetectable IgG4 levels, which is especially common in young children. Although several studies have shown that a large population of patients with recurrent respiratory tract infection have low IgG4 concentrations, the significance of this finding is not clear since a low concentration of IgG4 also occurs in a substantial percentage of healthy children (63,70).

TABLE IV Frequency (%) of decreased IgG subclass concentrations in adults

Sample Origin Number of samples IgG1 IgG2 IgG3 IgG4
Children 3854 4.9% 19.4% 6.3% 0.8%
Patients * 1175 28% 17% 13% 9%
Healthy individuals 162 8% 3% 1% 1%



4.3 IgG subclasses and allergy (85,86,87)

Among allergen-specific IgG antibodies in allergic individuals, there is a preponderance of IgG1 and IgG4, while IgG2 and IgG3 responses are small. Other findings in allergic patients include the following:

-Elevated IgG4 concentrations often occur in sera of patients with atopic eczema and dermatitis, probably as the result of prolonged antigenic stimulation (88).

-In allergy to many different allergens, allergen-specific IgG antibodies are predominantly of the IgG4 subclass and their levels increase during desensitisation therapy. In the antibody response to desensitization/immunotherapy, initially mainly IgG1 is formed, whereas IgG4 becomes more prominent after 1-2 years.

Allergen-specific IgG4 has often been regarded as a two-headed phenomenon: potentially harmful as well as potentially protective However, when more is found out about IgG4 antibodies, the harmful effects are hard to substantiate. The protective effects are still debated, but particularly from the field of parasitology the evidence is accumulating that IgG4 does, under certain conditions, effectively interfere with allergen-induced, IgE-medical effector cell triggering, i.e. IgG4 acts as a blocking antibody. Recent data indicate a striking similarity with respect to the type of antigen that triggers the IgG4 and IgE immune responses. Since a marked difference in epitope specificity exists between the IgG4 and IgE antibodies, only a fraction of the allergen-specific IgG4 can interfere effectively with IgE binding. The use of IgG4 antibody assays to monitor immunotherapy is justifiable, but its value should not be overrated. However, if no IgG4 antibody is induced by conventional immunotherapy, the therapy is likely to have been ineffective. An immunotherapy may be considered to be immunologically effective if a substantial increase (10 to 100 fold) in allergen-specific IgG4 is induced (89).

4.4 IgG subclasses in other diseases

Decreased or increased levels of IgG subclasses in serum are associated with several other diseases, examples of which will be given here (90).

4.4.1 Infectious diseases (6)

In most infections the first antibodies to appear will be of the IgM class, while those of the IgG class will be produced later. In general, microbial protein antigens will mainly evoke antibody responses of the IgG1 and IgG3 subclasses, with a minor contribution of IgG2 and IgG4. On the other hand, polysaccharide antigens will predominantly induce IgG2 antibodies.

Some disease-specific observations:

- Pneumococcal otitis media in children is associated with a decreased level of IgG2.
- Patients with recurrent infections by encapsulated bacteria often show decreased levels of IgG2 and IgG4.
- Recurrent respiratory infections with bronchiectasis are often associated with decreased levels of IgG2, IgG3 and IgG4.
- Cystic fibrosis with chronic Pseudomonas aeruginosa infection is associated with an increased level of IgG2 and IgG3, the latter of which seems to be of prognostic significance.


4.4.2 Autoimmunity

In autoimmune diseases the levels of IgG subclasses do mostly not differ from those in healthy individuals, but specific autoantibodies show variable subclass restrictions: frequently, autoantibodies are of the IgG1 and IgG3 subclasses (91,92,118).
- Human rheumatoid factors (RF) are defined as IgG, IgA or IgM antibodies against the Fc fragment of immunoglobulin. In most cases, RF have been found to bind to the Fc fragments of IgG. As for their subclass specificity, most RF have been shown to react with IgG1, followed by IgG2 and IgG4. Binding of RF to IgG3 is rare.

- Abnormal IgG1: IgG2 ratios have been reported in patients suffering from connective tissue diseases. In case of a selective polyclonal increase of IgG1, one should be alert for the possibility of Sjögren's syndrome. It has been suggested that this immunoglobulin abnormality is the product of a restricted oligoclonal B cell response and may thus be the consequence of a benign B cell lymphoma (93,94,95,96).

- Autoantibodies to neutrophil cytoplasmic antigens (ANCA) are predominantly of the IgG1 and IgG4 subclass (97,98). Autoantibodies of the IgG3 subclass almost exclusively occur in patients with renal involvement(98).

anilla
06-15-2011, 04:54 PM
thanks, everyone for the warm welcome! :)



IgG2: An IgG2 deficiency is offten associated with otitis media acuta and sinusitis, association with ataxia telangietasia and with System Lupus Erythematosus (SLE) has also been reported.

oh wow-- i also have low IGg2 (188). they haven't checked it in about a year, it may be lower now.


- Abnormal IgG1: IgG2 ratios have been reported in patients suffering from connective tissue diseases. In case of a selective polyclonal increase of IgG1, one should be alert for the possibility of Sjögren's syndrome. It has been suggested that this immunoglobulin abnormality is the product of a restricted oligoclonal B cell response and may thus be the consequence of a benign B cell lymphoma (93,94,95,96).

do we know what that ratio should be?



also-- i've had low vit D for a long time and it only keeps gong down-- no matter how many rx of 50k iu they give me. i've been deficient in B12 for which i got shots for 6 mos. was doing ok, but now seems to be declining again.

lovedbyHim
06-15-2011, 04:58 PM
Keep reading. Check out vit. D thread. Mine is dropping and I am on the same dose. It's amazing isn't it? Yep, you are not crazy. Glad your here.

Peridot20_Gem
06-15-2011, 05:26 PM
Anillia, properties of 1gG and 2gG and also look up the Vitamin D thread like Tammy mentioned and you should be on B12 Jabs for life lke myself if it's coming back.

2.3 Properties of human IgG subclasses

In the 1960's extensive studies, performed with specific polyclonal rabbit antisera against homogeneous human IgG myeloma proteins revealed the existence of four distinct subgroups of human IgG, which were designated IgG1, IgG2, IgG3 and IgG4, respectively (11,12,13). Since early studies were performed with polyclonal antisera, rendered specific by absorption, the amounts of specific reagents were relatively limited (14). In the 1980's, monoclonal antibodies against human IgG and its subclasses became available, which permitted more reproducible measurements and provided an improvement to studies dealing with IgG subclass levels in a variety of conditions (15,16,17).

Quantitatively, the relative serum concentrations of the human IgG subclasses are as follows (18,19): IgG1 > IgG2 > IgG3 = IgG4. The four subclasses show more than 95% homology in the amino acid sequences of the constant domains of the y-heavy chains. The four IgG subclasses show their most conspicuous differences in the amino acid composition and structure of the 'hinge region', which is the part of the molecule containing disulfide bonds between the y-heavy chains (figure 2). This region, between the Fab arms (Fragment antigen binding) and the two carboxy-terminal domains CH2 and CH3) of both heavy chains, determines the flexibility of the molecule (20,21). In the schematic structure of IgG, shown in figure 4, it is seen that the molecule contains domain-like structures, in which the two identical antigen-binding Fab fragments and the single Fc fragment (Fragment crystallisable) are quite mobile.

The upper hinge (towards the amino-terminal) segment allows variability of the angle between the Fab arms (Fab-Fab flexibility) as well as rotational flexibility of each individual Fab. The flexibility of the lower hinge region (towards the carboxy-terminal) directly determines the position of the Fab-arms relative to the Fc region (Fab-Fc flexibility). Hinge-dependent Fab-Fab and Fab-Fc flexibility may be important in triggering further effector functions such as complement activation and Fc receptor binding.

The length and flexibility of the hinge region varies among the IgG subclasses. The hinge region of IgG1 encompasses amino acids 216-231 and since it is freely flexible, the Fab fragments can rotate about their axes of symmetry and move within a sphere centered at the first of two inter-heavy chain disulfide bridges (23). IgG2 has a shorter hinge than IgG1, with 12 amino acid residues and four disulfide bridges. The hinge region of IgG2 lacks a glycine residue, it is relatively short and contains a rigid poly-proline double helix, stabilised by extra inter-heavy chain disulfide bridges. These properties restrict the flexibility of the IgG2 molecule (24). IgG3 differs from the other subclasses by its unique extended hinge region (about four times as long as the IgG1 hinge), containing 62 amino acids (including 21 prolines and 11 cysteines), forming an inflexible poly-proline double helix (25,26). In IgG3 the Fab fragments are relatively far away from the Fc fragment, giving the molecule a greater flexibility. The elongated hinge in IgG3 is also responsible for its higher molecular weight compared to the other subclasses. The hinge region of IgG4 is shorter than that of IgG1 and its flexibility is intermediate between that of IgG1 and IgG2. The schematic structure of the four IgG subclasses is shown in figure 5 (bottom of page).

As indicated in table 1, the four IgG subclasses differ with respect to the number of inter-heavy chain disulfide bonds in the hinge region (26). The structural differences between the IgG subclasses are also reflected in their susceptibility to proteolytic enzymes, such as papain (27), plasmin (28), trypsin (29) and pepsin (30).

IgG3 is very susceptible to cleavage by these enzymes, whereas IgG2 is relatively resistant. IgG1 and IgG4 exhibit an intermediary sensitivity, depending upon the enzyme used. Since these proteolytic enzymes all cleave IgG molecules near or within the hinge region, it is likely that the high sensitivity of IgG3 to enzyme digestion is related to its accessible hinge.

Another structural difference between the human IgG subclasses is the linkage of the heavy and light chain by a disulfide bond. This bond links the carboxy-terminal of the light chain with the cysteine residue at position 220 (in IgG) or at position 131 (in IgG2, IgG3 and IgG4) of the CH1 sequence of the heavy chain. Because in the folded structure these positions are close in space, they conserve the essential structure of the molecule.

In addition to differences among genes encoding the IgG subclass proteins, each with different amino acid composition and derived properties, mutations within these genes have led to variations of the composition of IgG subclass proteins within the population. The latter mutations provide the basis for genetic markers (called Gm allotypes) and correspond with minor differences in primary amino acid sequence between molecules of one IgG subclass that occur throughout a species. These allotypic determinants are polymorphic epitopes, which are inherited in a Mendelian pattern. Among individuals, different allelic forms are expressed. At present, immunoglobulin G can be typed for 18 different allotypes, located on the heavy chain. Subclass IgG3 is the most polymorphic, with thirteen Gm3 allotypes (31). There are four IgG1 allotypes and one IgG2 allotype, whereas no allotypes have been detected on the heavy chains of IgG4.Allotyping of immunoglobulins can be of diagnostic use in family and parenthood investigations (32,33).

steve.b
06-16-2011, 04:48 AM
hi anilla,
welcome to our family.

yes unfortunatelly, many of us have trouble with doctors. unless we fit there version of lupus, they will not commit.

remember there is 63 types of auto immune disorders, and many of the symptoms overlap.

as others have said, many of us find a pain diary very usefull.

read through a few of the threads, these subjects come up often.

again welcome.

samanthap6
06-25-2011, 02:20 PM
Hi I'm new here and I am positive I have sle it's just getting a diagnosis from a dr that's the problem. Well here's my story : As a child i was always outside swimming and playing. But when i think back i remember always being weak especially in the summer. Although i loved to swim i would come in exhausted! My mom says i was always sickly as a child. I almost died of chicken pox! My mom always tells me about them covering my entire body to the point they were on top of each other. Even in my mouth and ears. I have scars all over my body from them. That is when she noticed me staying tired and weak all the time. But i fought the fatigue so i could play with friends and family. Fast forward to the age of 16 I get married and have my 1st child at 17. That is where my battle begins! After my daughter was born premature i broke out in a rash all over! I thought i was allergic to something! But i was wrong! I went to about 20 dr's& specialist who had never seen a rash like this and nothing took it away but prednisone packs. But as soon as i would get off the pred. The rash was back! So i went from dr to dr who gave me pred because they couldn't figure out what the rash was from. I was on pred for 1-2years off and on. I also noticed my fatigue was getting worse. My hair started falling out and i was getting migraine headaches. I have had the rash since then just not as bad. I have had 5 more children also who all but the last one was premature. For the past 6 years the rash and fatigue has been horrible! I also became very sensitive to the sun and break out in hives. Even if i get a hot bath i come out shaking and the rash and hives get horrible! I have went down hill since i had my last baby in 2008. The rash has left scars all over me. And it comes and goes. I cant go in the sun at all. I get the butterfly rash if i go in the sun or get hot or upset. My hair is falling out in globs and im up all night with severe pain in my joints muscles and bones. I have the worst headaches that meds don't even help. I have had test after test done but ana is neg. Every time. My anticardiolipin igg was 10.1 but the normal range was 10.0 or below. The test results said high but dr said it was not because they repeated it and it was normal. My liver enzymes ast alt and sed rate crp have been elevated for years. My rbc are low my wbc are abnormal. I have raynauds. Low vitamin c d and b-12. I have high cholesterol ldl. I am hurting so bad i cant hardly walk. My wrists ankle hip shoulder and finger joints feel like they are broke. My knees are starting to bother me. I am only 29 and i seriously am thinking of using a wheelchair! I cant take much more pain. I have been to a pcp and rheumy who say nothing is wrong. But i should talk to a physciatrist about my pain and get more excercise! I couldn't believe what i was hearing!!!! These dr's work together might i add! My pcp also said i had blood in my urine. I also have a thyroid nodule and thyroiditis. If anyone on here know any good dr's in fl who will diagnose or even treat me without positive ana please im begging let me know! My husband and i are desperate for help before there is permanent damage to my organs!

tgal
06-25-2011, 03:59 PM
Hi I'm new here and I am positive I have sle it's just getting a diagnosis from a dr that's the problem. Well here's my story : As a child i was always outside swimming and playing. But when i think back i remember always being weak especially in the summer. Although i loved to swim i would come in exhausted! My mom says i was always sickly as a child. I almost died of chicken pox! My mom always tells me about them covering my entire body to the point they were on top of each other. Even in my mouth and ears. I have scars all over my body from them. That is when she noticed me staying tired and weak all the time. But i fought the fatigue so i could play with friends and family. Fast forward to the age of 16 I get married and have my 1st child at 17. That is where my battle begins! After my daughter was born premature i broke out in a rash all over! I thought i was allergic to something! But i was wrong! I went to about 20 dr's& specialist who had never seen a rash like this and nothing took it away but prednisone packs. But as soon as i would get off the pred. The rash was back! So i went from dr to dr who gave me pred because they couldn't figure out what the rash was from. I was on pred for 1-2years off and on. I also noticed my fatigue was getting worse. My hair started falling out and i was getting migraine headaches. I have had the rash since then just not as bad. I have had 5 more children also who all but the last one was premature. For the past 6 years the rash and fatigue has been horrible! I also became very sensitive to the sun and break out in hives. Even if i get a hot bath i come out shaking and the rash and hives get horrible! I have went down hill since i had my last baby in 2008. The rash has left scars all over me. And it comes and goes. I cant go in the sun at all. I get the butterfly rash if i go in the sun or get hot or upset. My hair is falling out in globs and im up all night with severe pain in my joints muscles and bones. I have the worst headaches that meds don't even help. I have had test after test done but ana is neg. Every time. My anticardiolipin igg was 10.1 but the normal range was 10.0 or below. The test results said high but dr said it was not because they repeated it and it was normal. My liver enzymes ast alt and sed rate crp have been elevated for years. My rbc are low my wbc are abnormal. I have raynauds. Low vitamin c d and b-12. I have high cholesterol ldl. I am hurting so bad i cant hardly walk. My wrists ankle hip shoulder and finger joints feel like they are broke. My knees are starting to bother me. I am only 29 and i seriously am thinking of using a wheelchair! I cant take much more pain. I have been to a pcp and rheumy who say nothing is wrong. But i should talk to a physciatrist about my pain and get more excercise! I couldn't believe what i was hearing!!!! These dr's work together might i add! My pcp also said i had blood in my urine. I also have a thyroid nodule and thyroiditis. If anyone on here know any good dr's in fl who will diagnose or even treat me without positive ana please im begging let me know! My husband and i are desperate for help before there is permanent damage to my organs!

Stories like these make me so angry! I was in this situation at one time and there simply are no words to describe how wrong this is. I am not a doctor and I have no way to know if you have Lupus or not however there are a few signs in what you wrote that there is something going on and it could possibly autoimmune. The majority of people do not have raynaud's nor does their hair fall out. Actually, they don't have any of the things going on that you do. I believe the very first thing that you need to do is to get new doctors! You will see this often if you start reading through the old threads but it is very true. The doctors work for YOU and if they are not listening then it is time to fire them and hire new ones!

I hope you find some peace and comfort in our little home on the web. Make yourself at home and I look forward to getting to know you

steve.b
06-25-2011, 10:28 PM
welcome samantha,
i agree with mari. you pay the doctor bill. pay it to somreone who treats you seriously.

lovedbyHim
06-26-2011, 03:24 AM
Samantha, I would look for a lupus support network in Florida to see if they know of any good rheumys. I had to go through 4 until I found one that took the time to put all the pieces together. I pray you find someone who is good and see them ASAP. There is a lupus center in Pittsburgh, PA. I have heard good things about them. Perhaps you could go on line and get their number and call them to see if they know of any centers in Florida. I go to an orthopedic center and my rheumy is incredible. It is new and up to date. Perhaps you can look for a rheumy there. Bless you in your search.